diff --git a/tests/test_generate_popular_node_signatures.py b/tests/test_generate_popular_node_signatures.py
index f25107d..12023d1 100644
--- a/tests/test_generate_popular_node_signatures.py
+++ b/tests/test_generate_popular_node_signatures.py
@@ -2222,6 +2222,30 @@ globals()["GlobalsClassReturnTypesNode"].RETURN_TYPES.clear()
         self.assertEqual({}, result["nodes"])
         self.assertEqual("no_static_nodes", result["pack"]["status"])
 
+    def test_globals_get_class_return_types_mutation_after_mapping_skips_node(self):
+        source = '''
+class GlobalsGetReturnTypesNode:
+    RETURN_TYPES = ["IMAGE"]
+
+    @classmethod
+    def INPUT_TYPES(cls):
+        return {
+            "required": {
+                "image": ("IMAGE",),
+            },
+        }
+
+
+NODE_CLASS_MAPPINGS = {
+    "GlobalsGetReturnTypesNode": GlobalsGetReturnTypesNode,
+}
+globals().get("GlobalsGetReturnTypesNode").RETURN_TYPES.clear()
+'''
+        result = self._extract_source(source, "globals-get-return-types-pack")
+
+        self.assertEqual({}, result["nodes"])
+        self.assertEqual("no_static_nodes", result["pack"]["status"])
+
     def test_module_class_tuple_alias_patch_after_mapping_skips_node(self):
         source = '''
 class TupleAliasPatchedNode:
@@ -2346,6 +2370,30 @@ globals()["NODE_CLASS_MAPPINGS"].clear()
         self.assertEqual({}, result["nodes"])
         self.assertEqual("no_static_nodes", result["pack"]["status"])
 
+    def test_globals_update_invalidates_static_node_mapping(self):
+        source = '''
+class GlobalUpdateNode:
+    RETURN_TYPES = ("IMAGE",)
+
+    @classmethod
+    def INPUT_TYPES(cls):
+        return {
+            "required": {
+                "image": ("IMAGE",),
+            },
+        }
+
+
+NODE_CLASS_MAPPINGS = {
+    "GlobalUpdateNode": GlobalUpdateNode,
+}
+globals().update(NODE_CLASS_MAPPINGS={})
+'''
+        result = self._extract_source(source, "global-update-mapping-pack")
+
+        self.assertEqual({}, result["nodes"])
+        self.assertEqual("no_static_nodes", result["pack"]["status"])
+
     def test_unpacked_alias_mutation_invalidates_static_node_mapping(self):
         source = '''
 class UnpackedAliasMutatedMappingNode:
diff --git a/tools/generate_popular_node_signatures.py b/tools/generate_popular_node_signatures.py
index ff85e1d..5f9c018 100644
--- a/tools/generate_popular_node_signatures.py
+++ b/tools/generate_popular_node_signatures.py
@@ -37,6 +37,8 @@ _CONTROL_FLOW_TYPES = (ast.If, ast.For, ast.AsyncFor, ast.While, ast.Try, ast.Wi
 if hasattr(ast, "TryStar"):
     _CONTROL_FLOW_TYPES += (ast.TryStar,)
 _CLASS_SIGNATURE_ATTRS = {"INPUT_TYPES", "RETURN_NAMES", "RETURN_TYPES"}
+_DYNAMIC_NAMESPACE_MUTATION = object()
+_NAMESPACE_FUNCTIONS = {"globals", "locals", "vars"}
 
 
 def _literal(node, env, allow_mutable_env=True):
@@ -83,23 +85,46 @@ def _is_mutable_static_value(value):
     return isinstance(value, (dict, list, set))
 
 
+def _namespace_call_function_name(node):
+    if not isinstance(node, ast.Call):
+        return None
+    if not isinstance(node.func, ast.Name) or node.func.id not in _NAMESPACE_FUNCTIONS:
+        return None
+    if node.args or node.keywords:
+        return None
+    return node.func.id
+
+
 def _namespace_subscript_name(node):
     if not isinstance(node, ast.Subscript):
         return None
-    if not isinstance(node.value, ast.Call) or not isinstance(node.value.func, ast.Name):
-        return None
-    if node.value.func.id not in {"globals", "locals", "vars"}:
-        return None
-    if node.value.args or node.value.keywords:
+    if _namespace_call_function_name(node.value) is None:
         return None
     if isinstance(node.slice, ast.Constant) and isinstance(node.slice.value, str):
         return node.slice.value
     return None
 
 
+def _namespace_lookup_name(node):
+    if not isinstance(node, ast.Call):
+        return None
+    if not isinstance(node.func, ast.Attribute) or node.func.attr != "get":
+        return None
+    if _namespace_call_function_name(node.func.value) is None:
+        return None
+    if not node.args:
+        return None
+    if isinstance(node.args[0], ast.Constant) and isinstance(node.args[0].value, str):
+        return node.args[0].value
+    return None
+
+
 def _target_names(target):
     if isinstance(target, ast.Name):
         return {target.id}
+    if isinstance(target, ast.Call):
+        name = _namespace_lookup_name(target)
+        return {name} if name is not None else set()
     if isinstance(target, (ast.List, ast.Tuple)):
         names = set()
         for item in target.elts:
@@ -119,6 +144,9 @@ def _target_names(target):
 
 def _root_name(node):
     while True:
+        name = _namespace_lookup_name(node)
+        if name is not None:
+            return name
         name = _namespace_subscript_name(node)
         if name is not None:
             return name
@@ -167,6 +195,33 @@ def _getattr_mutating_method_target_names(node):
     return _target_names(getattr_call.args[0])
 
 
+def _namespace_mutating_call_target_names(node):
+    if not isinstance(node, ast.Call):
+        return set()
+    if not isinstance(node.func, ast.Attribute):
+        return set()
+    if _namespace_call_function_name(node.func.value) is None:
+        return set()
+    if node.func.attr not in _MUTATING_METHODS:
+        return set()
+    if node.func.attr != "update":
+        return {_DYNAMIC_NAMESPACE_MUTATION}
+
+    names = set()
+    for keyword in node.keywords:
+        if keyword.arg is None:
+            names.add(_DYNAMIC_NAMESPACE_MUTATION)
+        else:
+            names.add(keyword.arg)
+    if node.args or not names:
+        names.add(_DYNAMIC_NAMESPACE_MUTATION)
+    return names
+
+
+def _name_invalidated_by(name, names):
+    return name in names or _DYNAMIC_NAMESPACE_MUTATION in names
+
+
 def _attribute_target_base_names(target):
     if isinstance(target, ast.Attribute):
         name = _root_name(target.value)
@@ -259,6 +314,7 @@ def _class_attribute_mutation_target_names(stmt):
         def visit_Call(self, node):
             names.update(_setattr_delattr_target_names(node))
             names.update(_getattr_mutating_method_target_names(node))
+            names.update(_namespace_mutating_call_target_names(node))
             if isinstance(node.func, ast.Attribute) and node.func.attr in _MUTATING_METHODS:
                 names.update(_attribute_target_base_names(node.func.value))
             self.generic_visit(node)
@@ -428,6 +484,7 @@ def _mutating_call_target_names(stmt):
         def visit_Call(self, node):
             names.update(_setattr_delattr_target_names(node))
             names.update(_getattr_mutating_method_target_names(node))
+            names.update(_namespace_mutating_call_target_names(node))
             if isinstance(node.func, ast.Attribute) and node.func.attr in _MUTATING_METHODS:
                 names.update(_target_names(node.func.value))
             self.generic_visit(node)
@@ -550,8 +607,13 @@ def _invalidate_class_bindings(class_bindings, names):
 
 def _apply_module_stmt_to_env(stmt, env, class_bindings=None):
     names = _mutating_call_target_names(stmt)
-    _invalidate_class_bindings(class_bindings, names)
-    _invalidate_env_names(env, names)
+    if _DYNAMIC_NAMESPACE_MUTATION in names:
+        env.clear()
+        if class_bindings is not None:
+            class_bindings.clear()
+    else:
+        _invalidate_class_bindings(class_bindings, names)
+        _invalidate_env_names(env, names)
     if isinstance(stmt, ast.ClassDef):
         if class_bindings is not None:
             if stmt.decorator_list:
@@ -1127,7 +1189,7 @@ def _final_module_dict(tree, name, value_converter, value_invalidated_by_names=N
             and value_invalidated_by_names(value, class_attr_names)
         ):
             value = _INVALID
-        if name in _mutating_call_target_names(stmt):
+        if _name_invalidated_by(name, _mutating_call_target_names(stmt)):
             value = _INVALID
         if _module_dict_alias_invalidated(stmt, module_dict_aliases):
             value = _INVALID