diff --git a/Lib/profiling/sampling/__main__.py b/Lib/profiling/sampling/__main__.py
index 47bd3a0113eb3d..a45b645eae05fc 100644
--- a/Lib/profiling/sampling/__main__.py
+++ b/Lib/profiling/sampling/__main__.py
@@ -46,6 +46,7 @@
 """
 
 from .cli import main
+from .errors import SamplingUnknownProcessError, SamplingModuleNotFoundError, SamplingScriptNotFoundError
 
 def handle_permission_error():
     """Handle PermissionError by displaying appropriate error message."""
@@ -64,3 +65,9 @@ def handle_permission_error():
         main()
     except PermissionError:
         handle_permission_error()
+    except SamplingUnknownProcessError as err:
+        print(f"Tachyon cannot find the process: {err}", file=sys.stderr)
+        sys.exit(1)
+    except (SamplingModuleNotFoundError, SamplingScriptNotFoundError) as err:
+        print(f"Tachyon cannot find the target: {err}", file=sys.stderr)
+        sys.exit(1)
diff --git a/Lib/profiling/sampling/cli.py b/Lib/profiling/sampling/cli.py
index e1ff3758c0d341..554167e43f5ed8 100644
--- a/Lib/profiling/sampling/cli.py
+++ b/Lib/profiling/sampling/cli.py
@@ -10,7 +10,8 @@
 import time
 from contextlib import nullcontext
 
-from .sample import sample, sample_live
+from .errors import SamplingUnknownProcessError, SamplingModuleNotFoundError, SamplingScriptNotFoundError
+from .sample import sample, sample_live, _is_process_running
 from .pstats_collector import PstatsCollector
 from .stack_collector import CollapsedStackCollector, FlamegraphCollector
 from .heatmap_collector import HeatmapCollector
@@ -743,6 +744,8 @@ def main():
 
 def _handle_attach(args):
     """Handle the 'attach' command."""
+    if not _is_process_running(args.pid):
+        raise SamplingUnknownProcessError(args.pid)
     # Check if live mode is requested
     if args.live:
         _handle_live_attach(args, args.pid)
@@ -792,13 +795,13 @@ def _handle_run(args):
             added_cwd = True
         try:
             if importlib.util.find_spec(args.target) is None:
-                sys.exit(f"Error: Module not found: {args.target}")
+                raise SamplingModuleNotFoundError(args.target)
         finally:
             if added_cwd:
                 sys.path.remove(cwd)
     else:
         if not os.path.exists(args.target):
-            sys.exit(f"Error: Script not found: {args.target}")
+            raise SamplingScriptNotFoundError(args.target)
 
     # Check if live mode is requested
     if args.live:
diff --git a/Lib/profiling/sampling/errors.py b/Lib/profiling/sampling/errors.py
new file mode 100644
index 00000000000000..0246f201f21d5d
--- /dev/null
+++ b/Lib/profiling/sampling/errors.py
@@ -0,0 +1,23 @@
+"""Custom exceptions for the sampling profiler."""
+
+class SamplingProfilerError(Exception):
+    """Base exception for sampling profiler errors."""
+
+class SamplingPermissionError(SamplingProfilerError):
+    def __init__(self):
+        super().__init__(f"Insufficient permission to access process.")
+
+class SamplingUnknownProcessError(SamplingProfilerError):
+    def __init__(self, pid):
+        self.pid = pid
+        super().__init__(f"Process with PID '{pid}' does not exist.")
+
+class SamplingScriptNotFoundError(SamplingProfilerError):
+    def __init__(self, script_path):
+        self.script_path = script_path
+        super().__init__(f"Script '{script_path}' not found.")
+
+class SamplingModuleNotFoundError(SamplingProfilerError):
+    def __init__(self, module_name):
+        self.module_name = module_name
+        super().__init__(f"Module '{module_name}' not found.")
diff --git a/Lib/profiling/sampling/sample.py b/Lib/profiling/sampling/sample.py
index 294ec3003fc6bc..12506d694885fb 100644
--- a/Lib/profiling/sampling/sample.py
+++ b/Lib/profiling/sampling/sample.py
@@ -34,23 +34,29 @@ def __init__(self, pid, sample_interval_usec, all_threads, *, mode=PROFILING_MOD
         self.all_threads = all_threads
         self.mode = mode  # Store mode for later use
         self.collect_stats = collect_stats
+        try:
+            self.unwinder = self._new_unwinder(native, gc, opcodes, skip_non_matching_threads)
+        except RuntimeError as err:
+            raise SystemExit(err)
+        # Track sample intervals and total sample count
+        self.sample_intervals = deque(maxlen=100)
+        self.total_samples = 0
+        self.realtime_stats = False
+
+    def _new_unwinder(self, native, gc, opcodes, skip_non_matching_threads):
         if _FREE_THREADED_BUILD:
-            self.unwinder = _remote_debugging.RemoteUnwinder(
-                self.pid, all_threads=self.all_threads, mode=mode, native=native, gc=gc,
+            unwinder = _remote_debugging.RemoteUnwinder(
+                self.pid, all_threads=self.all_threads, mode=self.mode, native=native, gc=gc,
                 opcodes=opcodes, skip_non_matching_threads=skip_non_matching_threads,
-                cache_frames=True, stats=collect_stats
+                cache_frames=True, stats=self.collect_stats
             )
         else:
-            only_active_threads = bool(self.all_threads)
-            self.unwinder = _remote_debugging.RemoteUnwinder(
-                self.pid, only_active_thread=only_active_threads, mode=mode, native=native, gc=gc,
+            unwinder = _remote_debugging.RemoteUnwinder(
+                self.pid, only_active_thread=bool(self.all_threads), mode=self.mode, native=native, gc=gc,
                 opcodes=opcodes, skip_non_matching_threads=skip_non_matching_threads,
-                cache_frames=True, stats=collect_stats
+                cache_frames=True, stats=self.collect_stats
             )
-        # Track sample intervals and total sample count
-        self.sample_intervals = deque(maxlen=100)
-        self.total_samples = 0
-        self.realtime_stats = False
+        return unwinder
 
     def sample(self, collector, duration_sec=10, *, async_aware=False):
         sample_interval_sec = self.sample_interval_usec / 1_000_000
@@ -86,7 +92,7 @@ def sample(self, collector, duration_sec=10, *, async_aware=False):
                         collector.collect_failed_sample()
                         errors += 1
                     except Exception as e:
-                        if not self._is_process_running():
+                        if not _is_process_running(self.pid):
                             break
                         raise e from None
 
@@ -148,22 +154,6 @@ def sample(self, collector, duration_sec=10, *, async_aware=False):
                 f"({(expected_samples - num_samples) / expected_samples * 100:.2f}%)"
             )
 
-    def _is_process_running(self):
-        if sys.platform == "linux" or sys.platform == "darwin":
-            try:
-                os.kill(self.pid, 0)
-                return True
-            except ProcessLookupError:
-                return False
-        elif sys.platform == "win32":
-            try:
-                _remote_debugging.RemoteUnwinder(self.pid)
-            except Exception:
-                return False
-            return True
-        else:
-            raise ValueError(f"Unsupported platform: {sys.platform}")
-
     def _print_realtime_stats(self):
         """Print real-time sampling statistics."""
         if len(self.sample_intervals) < 2:
@@ -279,6 +269,25 @@ def _print_unwinder_stats(self):
             print(f"  {ANSIColors.YELLOW}Stale cache invalidations: {stale_invalidations}{ANSIColors.RESET}")
 
 
+def _is_process_running(pid):
+    if pid <= 0:
+        return False
+    if os.name == "posix":
+        try:
+            os.kill(pid, 0)
+            return True
+        except ProcessLookupError:
+            return False
+    elif sys.platform == "win32":
+        try:
+            _remote_debugging.RemoteUnwinder(pid)
+        except Exception:
+            return False
+        return True
+    else:
+        raise ValueError(f"Unsupported platform: {sys.platform}")
+
+
 def sample(
     pid,
     collector,
diff --git a/Lib/test/test_profiling/test_sampling_profiler/test_cli.py b/Lib/test/test_profiling/test_sampling_profiler/test_cli.py
index 4434335130c325..9b2b16d6e1965b 100644
--- a/Lib/test/test_profiling/test_sampling_profiler/test_cli.py
+++ b/Lib/test/test_profiling/test_sampling_profiler/test_cli.py
@@ -16,6 +16,7 @@
 from test.support import is_emscripten, requires_remote_subprocess_debugging
 
 from profiling.sampling.cli import main
+from profiling.sampling.errors import SamplingScriptNotFoundError, SamplingModuleNotFoundError, SamplingUnknownProcessError
 
 
 class TestSampleProfilerCLI(unittest.TestCase):
@@ -203,12 +204,12 @@ def test_cli_mutually_exclusive_pid_script(self):
         with (
             mock.patch("sys.argv", test_args),
             mock.patch("sys.stderr", io.StringIO()) as mock_stderr,
-            self.assertRaises(SystemExit) as cm,
+            self.assertRaises(SamplingScriptNotFoundError) as cm,
         ):
             main()
 
         # Verify the error is about the non-existent script
-        self.assertIn("12345", str(cm.exception.code))
+        self.assertIn("12345", str(cm.exception))
 
     def test_cli_no_target_specified(self):
         # In new CLI, must specify a subcommand
@@ -436,6 +437,7 @@ def test_cli_default_collapsed_filename(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             main()
@@ -475,6 +477,7 @@ def test_cli_custom_output_filenames(self):
         for test_args, expected_filename, expected_format in test_cases:
             with (
                 mock.patch("sys.argv", test_args),
+                mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
                 mock.patch("profiling.sampling.cli.sample") as mock_sample,
             ):
                 main()
@@ -513,6 +516,7 @@ def test_argument_parsing_basic(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             main()
@@ -534,6 +538,7 @@ def test_sort_options(self):
 
             with (
                 mock.patch("sys.argv", test_args),
+                mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
                 mock.patch("profiling.sampling.cli.sample") as mock_sample,
             ):
                 main()
@@ -547,6 +552,7 @@ def test_async_aware_flag_defaults_to_running(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             main()
@@ -562,6 +568,7 @@ def test_async_aware_with_async_mode_all(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             main()
@@ -576,6 +583,7 @@ def test_async_aware_default_is_none(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             main()
@@ -697,14 +705,20 @@ def test_async_aware_incompatible_with_all_threads(self):
     def test_run_nonexistent_script_exits_cleanly(self):
         """Test that running a non-existent script exits with a clean error."""
         with mock.patch("sys.argv", ["profiling.sampling.cli", "run", "/nonexistent/script.py"]):
-            with self.assertRaises(SystemExit) as cm:
+            with self.assertRaisesRegex(SamplingScriptNotFoundError, "Script '[\\w/.]+' not found."):
                 main()
-        self.assertIn("Script not found", str(cm.exception.code))
 
     @unittest.skipIf(is_emscripten, "subprocess not available")
     def test_run_nonexistent_module_exits_cleanly(self):
         """Test that running a non-existent module exits with a clean error."""
         with mock.patch("sys.argv", ["profiling.sampling.cli", "run", "-m", "nonexistent_module_xyz"]):
-            with self.assertRaises(SystemExit) as cm:
+            with self.assertRaisesRegex(SamplingModuleNotFoundError, "Module '[\\w/.]+' not found."):
+                main()
+
+    def test_cli_attach_nonexistent_pid(self):
+        fake_pid = "99999"
+        with mock.patch("sys.argv", ["profiling.sampling.cli", "attach", fake_pid]):
+            with self.assertRaises(SamplingUnknownProcessError) as cm:
                 main()
-        self.assertIn("Module not found", str(cm.exception.code))
+
+            self.assertIn(fake_pid, str(cm.exception))
diff --git a/Lib/test/test_profiling/test_sampling_profiler/test_integration.py b/Lib/test/test_profiling/test_sampling_profiler/test_integration.py
index 08a96d7eb459f0..e7f6c59d5cb770 100644
--- a/Lib/test/test_profiling/test_sampling_profiler/test_integration.py
+++ b/Lib/test/test_profiling/test_sampling_profiler/test_integration.py
@@ -17,7 +17,7 @@
     import profiling.sampling.sample
     from profiling.sampling.pstats_collector import PstatsCollector
     from profiling.sampling.stack_collector import CollapsedStackCollector
-    from profiling.sampling.sample import SampleProfiler
+    from profiling.sampling.sample import SampleProfiler, _is_process_running
 except ImportError:
     raise unittest.SkipTest(
         "Test only runs when _remote_debugging is available"
@@ -602,7 +602,7 @@ def test_sample_target_module(self):
 @requires_remote_subprocess_debugging()
 class TestSampleProfilerErrorHandling(unittest.TestCase):
     def test_invalid_pid(self):
-        with self.assertRaises((OSError, RuntimeError)):
+        with self.assertRaises((SystemExit, PermissionError)):
             collector = PstatsCollector(sample_interval_usec=100, skip_idle=False)
             profiling.sampling.sample.sample(-1, collector, duration_sec=1)
 
@@ -638,7 +638,7 @@ def test_is_process_running(self):
                 sample_interval_usec=1000,
                 all_threads=False,
             )
-            self.assertTrue(profiler._is_process_running())
+            self.assertTrue(_is_process_running(profiler.pid))
             self.assertIsNotNone(profiler.unwinder.get_stack_trace())
             subproc.process.kill()
             subproc.process.wait()
@@ -647,7 +647,7 @@ def test_is_process_running(self):
             )
 
         # Exit the context manager to ensure the process is terminated
-        self.assertFalse(profiler._is_process_running())
+        self.assertFalse(_is_process_running(profiler.pid))
         self.assertRaises(
             ProcessLookupError, profiler.unwinder.get_stack_trace
         )
diff --git a/Lib/test/test_profiling/test_sampling_profiler/test_modes.py b/Lib/test/test_profiling/test_sampling_profiler/test_modes.py
index f1293544776bc3..247416389daa07 100644
--- a/Lib/test/test_profiling/test_sampling_profiler/test_modes.py
+++ b/Lib/test/test_profiling/test_sampling_profiler/test_modes.py
@@ -252,6 +252,7 @@ def test_gil_mode_validation(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             try:
@@ -313,6 +314,7 @@ def test_gil_mode_cli_argument_parsing(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             try:
@@ -432,6 +434,7 @@ def test_exception_mode_validation(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             try:
@@ -493,6 +496,7 @@ def test_exception_mode_cli_argument_parsing(self):
 
         with (
             mock.patch("sys.argv", test_args),
+            mock.patch("profiling.sampling.cli._is_process_running", return_value=True),
             mock.patch("profiling.sampling.cli.sample") as mock_sample,
         ):
             try:
diff --git a/Misc/NEWS.d/next/Library/2025-12-13-10-34-59.gh-issue-142654.fmm974.rst b/Misc/NEWS.d/next/Library/2025-12-13-10-34-59.gh-issue-142654.fmm974.rst
new file mode 100644
index 00000000000000..7bb14cb499d850
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2025-12-13-10-34-59.gh-issue-142654.fmm974.rst
@@ -0,0 +1,2 @@
+Show the clearer error message when using ``profiling.sampling`` on an
+unknown PID.