diff --git a/mypy/checker.py b/mypy/checker.py
index 9c10cd2fc30d..8ff921996121 100644
--- a/mypy/checker.py
+++ b/mypy/checker.py
@@ -115,6 +115,7 @@
     RaiseStmt,
     RefExpr,
     ReturnStmt,
+    SetExpr,
     StarExpr,
     Statement,
     StrExpr,
@@ -5928,20 +5929,37 @@ def has_no_custom_eq_checks(t: Type) -> bool:
                             ):
                                 if_map[operands[left_index]] = remove_optional(item_type)
 
+                    right_iterable_expr = operands[right_index]
                     if right_index in narrowable_operand_index_to_hash:
                         if_type, else_type = self.conditional_types_for_iterable(
                             item_type, iterable_type
                         )
-                        expr = operands[right_index]
                         if if_type is None:
                             if_map = None
                         else:
-                            if_map[expr] = if_type
+                            if_map[right_iterable_expr] = if_type
                         if else_type is None:
                             else_map = None
                         else:
-                            else_map[expr] = else_type
+                            else_map[right_iterable_expr] = else_type
 
+                    # check for `None in <some_iterable>`
+                    if (
+                        isinstance(get_proper_type(item_type), NoneType)
+                        and isinstance(right_iterable_expr, (ListExpr, TupleExpr, SetExpr))
+                        # Ensure the iterable does not inherently contain None literals
+                        and not any(
+                            is_literal_none(iterable_item)
+                            for iterable_item in right_iterable_expr.items
+                        )
+                    ):
+                        if else_map is None:
+                            else_map = {}
+                        for iterable_item in right_iterable_expr.items:
+                            proper_item_type = self.lookup_type(iterable_item)
+                            # Remove the option of the current item to be `None` for the entire else scope
+                            if is_overlapping_none(proper_item_type):
+                                else_map[iterable_item] = remove_optional(proper_item_type)
                 else:
                     if_map = {}
                     else_map = {}
@@ -6006,8 +6024,8 @@ def has_no_custom_eq_checks(t: Type) -> bool:
                 and_conditional_maps(left_else_vars, right_else_vars),
             )
         elif isinstance(node, UnaryExpr) and node.op == "not":
-            left, right = self.find_isinstance_check(node.expr)
-            return right, left
+            left, iterable_expr = self.find_isinstance_check(node.expr)
+            return iterable_expr, left
         elif (
             literal(node) == LITERAL_TYPE
             and self.has_type(node)
diff --git a/test-data/unit/check-optional.test b/test-data/unit/check-optional.test
index 70f3c4486e14..98d7f93092cf 100644
--- a/test-data/unit/check-optional.test
+++ b/test-data/unit/check-optional.test
@@ -93,6 +93,71 @@ else:
   reveal_type(x)  # N: Revealed type is "Any"
 [builtins fixtures/bool.pyi]
 
+[case testRefinementAfterNoneInCheck]
+from typing import Optional, List
+
+def refine_types(a: Optional[int], b: Optional[str], c: Optional[float]) -> str:
+    if None in [a, b, c]:
+        return "One or more are None"
+    else:
+        reveal_type(a)  # N: Revealed type is "builtins.int"
+        reveal_type(b)  # N: Revealed type is "builtins.str"
+        reveal_type(c)  # N: Revealed type is "builtins.float"
+        return f"{a}, {b}, {c}"
+
+a: Optional[int] = 5
+b: Optional[str] = "hello"
+c: Optional[float] = None
+
+result = refine_types(a, b, c)
+reveal_type(result)  # N: Revealed type is "builtins.str"
+
+[case testRefinementWithComplexCondition]
+from typing import Optional, List
+
+def refine_complex(a: Optional[int], b: Optional[float], c: Optional[str]) -> str:
+    # Test with complex conditions mixed with `None in`
+    if None not in (a, b, c) and b + 3 != 5.5:
+        reveal_type(a)  # N: Revealed type is "builtins.int"
+        reveal_type(b)  # N: Revealed type is "builtins.float"
+        reveal_type(c)  # N: Revealed type is "builtins.str"
+        return f"{a}, {b}, {c}"
+    reveal_type(a)  # N: Revealed type is "Union[builtins.int, None]"
+    reveal_type(b)  # N: Revealed type is "Union[builtins.float, None]"
+    reveal_type(c)  # N: Revealed type is "Union[builtins.str, None]"
+    return "All are valid"
+
+a: Optional[int] = 5
+b: Optional[float] = 10.3
+c: Optional[str] = "cCCCc"
+
+result_complex = refine_complex(a, b, c)
+reveal_type(result_complex)  # N: Revealed type is "builtins.str"
+
+[case testRefinementFailureWhenNonePresent]
+from typing import Optional, List
+
+def check_failure(a: Optional[int], b: Optional[float], c: Optional[str]) -> str:
+    if None in {a, b, c}:
+        print(a + 3)            # E: Unsupported operand types for + ("None" and "int")  [operator]
+        print(b.is_integer())   # E: Item "None" of "float | None" has no attribute "is_integer"  [union-attr]
+        print(c.upper())        # E: Item "None" of "str | None" has no attribute "upper"  [union-attr]
+        return "None is present"
+    else:
+        print(a + 3)
+        print(b.is_integer())
+        print(c.upper())
+        return "All are valid"
+
+[case testNotRefiningWhenNoneIsInTheIterable]
+def not_refine_none_in_iterable(a: Optional[int], b: Optional[float], c: Optional[str]) -> str:
+    # Test with complex conditions mixed with `None in`
+    if None not in {a, b, c, None} and b + 3 != 5.5:  # E: Unsupported operand types for + ("None" and "int")
+        reveal_type(a)  # N: Revealed type is "Union[builtins.int, None]"
+        reveal_type(b)  # N: Revealed type is "Union[builtins.float, None]"
+        reveal_type(c)  # N: Revealed type is "Union[builtins.str, None]"
+    return "Bla Bla"
+
 [case testOrCases]
 from typing import Optional
 x = None  # type: Optional[str]