diff --git a/pkgs/by-name/wa/wasmtime/package.nix b/pkgs/by-name/wa/wasmtime/package.nix
index 00547218c2e9..a8be07cbe92c 100644
--- a/pkgs/by-name/wa/wasmtime/package.nix
+++ b/pkgs/by-name/wa/wasmtime/package.nix
@@ -13,20 +13,20 @@
 }:
 rustPlatform.buildRustPackage (finalAttrs: {
   pname = "wasmtime";
-  version = "44.0.1";
+  version = "45.0.0";
 
   src = fetchFromGitHub {
     owner = "bytecodealliance";
     repo = "wasmtime";
     tag = "v${finalAttrs.version}";
-    hash = "sha256-nVE18URbDKIrZr7ImPf2Zx5Ftq/oT2mZU0CMuBh+EYE=";
+    hash = "sha256-oCIMfBGhWZiaNNfH7Pc9DCpbEXs8AU3w8tIE6o/vjLk=";
     fetchSubmodules = true;
   };
 
   # Disable cargo-auditable until https://github.com/rust-secure-code/cargo-auditable/issues/124 is solved.
   auditable = false;
 
-  cargoHash = "sha256-K2Y6atvbvqIuc7Upk4134fZW1y329DlG2gzm8VveyWA=";
+  cargoHash = "sha256-yAPs2o2ayxxh3jk5+T8DiP9uFjBGyPTLzgP/RXPSj2g=";
   cargoBuildFlags = [
     "--package"
     "wasmtime-cli"
diff --git a/pkgs/development/python-modules/wasmtime/default.nix b/pkgs/development/python-modules/wasmtime/default.nix
index 5153d709f86e..dd3a0227db1e 100644
--- a/pkgs/development/python-modules/wasmtime/default.nix
+++ b/pkgs/development/python-modules/wasmtime/default.nix
@@ -18,14 +18,14 @@ let
 in
 buildPythonPackage (finalAttrs: {
   pname = "wasmtime";
-  version = "44.0.0";
+  version = "45.0.0";
   pyproject = true;
 
   src = fetchFromGitHub {
     owner = "bytecodealliance";
     repo = "wasmtime-py";
     tag = finalAttrs.version;
-    hash = "sha256-7K0j4jMsRB7/wNIj0pXxFTy0y7aN37wgCD1XKM92Ayw=";
+    hash = "sha256-XlAWPJB34uE+hbEMGZ46Ll6kXP+/lZ2amTKdjslGrP4=";
   };
 
   postPatch = ''
@@ -33,8 +33,9 @@ buildPythonPackage (finalAttrs: {
       --replace-fail "setuptools-git-versioning>=2.0,<3" "setuptools-git-versioning" \
       --replace-fail 'build-backend = "backend"' 'build-backend = "setuptools.build_meta"'
 
-    substituteInPlace ci/cbindgen.py \
-      --replace-fail "'-D__builtin_va_list=int'," "'-D__builtin_va_list=int', '-Dnullptr_t=void*',"
+    # `wasmtime/_{extern,types,value}.py` erroneously report unreachable statements
+    substituteInPlace mypy.ini \
+      --replace-fail "warn_unreachable = True" "warn_unreachable = False"
 
     # Don't run mypy via pytest-mypy (type checking breaks easily)
     substituteInPlace pytest.ini \
@@ -66,15 +67,17 @@ buildPythonPackage (finalAttrs: {
     writableTmpDirAsHomeHook
   ];
 
-  disabledTestPaths = [
-    "ci/cbindgen.py"
-  ];
-
   pythonImportsCheck = [ "wasmtime" ];
 
   preCheck = ''
     # cbindgen.py checks bindings against C headers during test collection.
     ln -s ${lib.getDev pkgs.wasmtime}/include wasmtime/include
+
+    # hardening options interfere with pycparser's CC call
+    export NIX_HARDENING_ENABLE=""
+
+    # $out is first in path which causes "import file mismatch"
+    export PYTHONPATH="$PWD:$PYTHONPATH"
   '';
 
   meta = {