diff --git a/lib/modules/manager/pep621/extract.spec.ts b/lib/modules/manager/pep621/extract.spec.ts
index 63aa8bcbdd11ff..4911bc35b732ad 100644
--- a/lib/modules/manager/pep621/extract.spec.ts
+++ b/lib/modules/manager/pep621/extract.spec.ts
@@ -281,6 +281,13 @@ describe('modules/manager/pep621/extract', () => {
           depType: 'project.dependencies',
           packageName: 'requests',
         },
+        {
+          datasource: 'pypi',
+          depName: 'hatchling',
+          depType: 'build-system.requires',
+          packageName: 'hatchling',
+          skipReason: 'unspecified-version',
+        },
         {
           currentValue: '==6.5',
           datasource: 'pypi',
@@ -323,5 +330,43 @@ describe('modules/manager/pep621/extract', () => {
       const res = extractPackageFile(content, 'pyproject.toml');
       expect(res?.packageFileVersion).toBe('0.0.2');
     });
+
+    it('should extract dependencies from build-system.requires', function () {
+      const content = codeBlock`
+        [build-system]
+        requires = ["hatchling==1.18.0", "setuptools==69.0.3"]
+        build-backend = "hatchling.build"
+
+        [project]
+        name = "test"
+        version = "0.0.2"
+        dependencies = [ "requests==2.30.0" ]
+      `;
+      const result = extractPackageFile(content, 'pyproject.toml');
+
+      expect(result?.deps).toEqual([
+        {
+          currentValue: '==2.30.0',
+          datasource: 'pypi',
+          depName: 'requests',
+          depType: 'project.dependencies',
+          packageName: 'requests',
+        },
+        {
+          currentValue: '==1.18.0',
+          datasource: 'pypi',
+          depName: 'hatchling',
+          depType: 'build-system.requires',
+          packageName: 'hatchling',
+        },
+        {
+          currentValue: '==69.0.3',
+          datasource: 'pypi',
+          depName: 'setuptools',
+          depType: 'build-system.requires',
+          packageName: 'setuptools',
+        },
+      ]);
+    });
   });
 });
diff --git a/lib/modules/manager/pep621/extract.ts b/lib/modules/manager/pep621/extract.ts
index d1f8e4accf7bf2..66648663dcddaf 100644
--- a/lib/modules/manager/pep621/extract.ts
+++ b/lib/modules/manager/pep621/extract.ts
@@ -43,6 +43,12 @@ export function extractPackageFile(
       def.project?.['optional-dependencies'],
     ),
   );
+  deps.push(
+    ...parseDependencyList(
+      depTypes.buildSystemRequires,
+      def['build-system']?.requires,
+    ),
+  );
 
   // process specific tool sets
   let processedDeps = deps;
diff --git a/lib/modules/manager/pep621/readme.md b/lib/modules/manager/pep621/readme.md
index 344e3948559e4e..3d3009e5b55856 100644
--- a/lib/modules/manager/pep621/readme.md
+++ b/lib/modules/manager/pep621/readme.md
@@ -9,5 +9,6 @@ Available `depType`s:
 
 - `project.dependencies`
 - `project.optional-dependencies`
+- `build-system.requires`
 - `tool.pdm.dev-dependencies`
 - `tool.hatch.envs.<env-name>`
diff --git a/lib/modules/manager/pep621/schema.ts b/lib/modules/manager/pep621/schema.ts
index 880336adb38dc5..212a1301c1b257 100644
--- a/lib/modules/manager/pep621/schema.ts
+++ b/lib/modules/manager/pep621/schema.ts
@@ -16,6 +16,11 @@ export const PyProjectSchema = z.object({
       'optional-dependencies': DependencyRecordSchema,
     })
     .optional(),
+  'build-system': z
+    .object({
+      requires: DependencyListSchema,
+    })
+    .optional(),
   tool: z
     .object({
       pdm: z
diff --git a/lib/modules/manager/pep621/utils.ts b/lib/modules/manager/pep621/utils.ts
index 4420992bcb4f43..5b28541993508f 100644
--- a/lib/modules/manager/pep621/utils.ts
+++ b/lib/modules/manager/pep621/utils.ts
@@ -15,6 +15,7 @@ export const depTypes = {
   dependencies: 'project.dependencies',
   optionalDependencies: 'project.optional-dependencies',
   pdmDevDependencies: 'tool.pdm.dev-dependencies',
+  buildSystemRequires: 'build-system.requires',
 };
 
 export function parsePEP508(