diff --git a/Lib/profiling/sampling/_sync_coordinator.py b/Lib/profiling/sampling/_sync_coordinator.py
index 8716e654104791..20b50ba9d9063d 100644
--- a/Lib/profiling/sampling/_sync_coordinator.py
+++ b/Lib/profiling/sampling/_sync_coordinator.py
@@ -10,6 +10,7 @@
 import socket
 import runpy
 import time
+import types
 from typing import List, NoReturn
 
 
@@ -175,15 +176,21 @@ def _execute_script(script_path: str, script_args: List[str], cwd: str) -> None:
     try:
         with open(script_path, 'rb') as f:
             source_code = f.read()
+
     except FileNotFoundError as e:
         raise TargetError(f"Script file not found: {script_path}") from e
     except PermissionError as e:
         raise TargetError(f"Permission denied reading script: {script_path}") from e
 
     try:
-        # Compile and execute the script
+        # gh-140729: Create a __mp_main__ module to allow pickling
+        main_module = types.ModuleType("__main__")
+        main_module.__file__ = script_path
+        main_module.__builtins__ = __builtins__
+        sys.modules['__main__'] = sys.modules['__mp_main__'] = main_module
+
         code = compile(source_code, script_path, 'exec')
-        exec(code, {'__name__': '__main__', '__file__': script_path})
+        exec(code, main_module.__dict__)
     except SyntaxError as e:
         raise TargetError(f"Syntax error in script {script_path}: {e}") from e
     except SystemExit:
diff --git a/Lib/test/test_profiling/test_sampling_profiler.py b/Lib/test/test_profiling/test_sampling_profiler.py
index cbfb21d3512eee..ad5bafaf7b82f4 100644
--- a/Lib/test/test_profiling/test_sampling_profiler.py
+++ b/Lib/test/test_profiling/test_sampling_profiler.py
@@ -22,7 +22,13 @@
 from profiling.sampling.gecko_collector import GeckoCollector
 
 from test.support.os_helper import unlink
-from test.support import force_not_colorized_test_class, SHORT_TIMEOUT
+from test.support import (
+    force_not_colorized_test_class,
+    SHORT_TIMEOUT,
+    script_helper,
+    os_helper,
+    SuppressCrashReport,
+)
 from test.support.socket_helper import find_unused_port
 from test.support import requires_subprocess, is_emscripten
 from test.support import captured_stdout, captured_stderr
@@ -3007,5 +3013,49 @@ def test_parse_mode_function(self):
             profiling.sampling.sample._parse_mode("invalid")
 
 
+@requires_subprocess()
+@skip_if_not_supported
+class TestProcessPoolExecutorSupport(unittest.TestCase):
+    """
+    Test that ProcessPoolExecutor works correctly with profiling.sampling.
+    """
+
+    def test_process_pool_executor_pickle(self):
+        # gh-140729: test use ProcessPoolExecutor.map() can sampling
+        test_script = '''
+import concurrent.futures
+
+def worker(x):
+    return x * 2
+
+if __name__ == "__main__":
+    with concurrent.futures.ProcessPoolExecutor() as executor:
+        results = list(executor.map(worker, [1, 2, 3]))
+        print(f"Results: {results}")
+'''
+        with os_helper.temp_dir() as temp_dir:
+            script = script_helper.make_script(
+                temp_dir, 'test_process_pool_executor_pickle', test_script
+            )
+            with SuppressCrashReport():
+                with script_helper.spawn_python(
+                    "-m", "profiling.sampling.sample",
+                    "-d", "5",
+                    "-i", "100000",
+                    script,
+                    stderr=subprocess.PIPE,
+                    text=True
+                ) as proc:
+                    proc.wait(timeout=SHORT_TIMEOUT)
+                    stdout = proc.stdout.read()
+                    stderr = proc.stderr.read()
+
+        if "PermissionError" in stderr:
+            self.skipTest("Insufficient permissions for remote profiling")
+
+        self.assertIn("Results: [2, 4, 6]", stdout)
+        self.assertNotIn("Can't pickle", stderr)
+
+
 if __name__ == "__main__":
     unittest.main()
diff --git a/Misc/NEWS.d/next/Core_and_Builtins/2025-10-29-11-31-59.gh-issue-140729.t9JsNt.rst b/Misc/NEWS.d/next/Core_and_Builtins/2025-10-29-11-31-59.gh-issue-140729.t9JsNt.rst
new file mode 100644
index 00000000000000..6725547667fb3c
--- /dev/null
+++ b/Misc/NEWS.d/next/Core_and_Builtins/2025-10-29-11-31-59.gh-issue-140729.t9JsNt.rst
@@ -0,0 +1,2 @@
+Fix pickling error in the sampling profiler when using ``concurrent.futures.ProcessPoolExecutor``
+script can not be properly pickled and executed in worker processes.