Cardiovascular　disease　(CVD)　is　a　global　health　problem　and　is　thought　to　be　responsible　for　almost　half　of　all　deaths　in　the　world.　Nevertheless,　currently　available　diagnostic　methods　for　CVD　are　strongly　depended　on　clinical　observation　and　monitoring,　which　commonly　result　in　false　diagnosis.　Herein,　an　attractive　strategy　of　a　metal-organic　framework　(MOF)　nanofilm-based　laser　desorption/ionization　mass　spectrometry　(LDI-MS)　was　developed　for　enhancing　serum　metabolic　profiling,　which　could　provide　precise　diagnosis　and　molecular　subtyping　of　CVD.　The　porous　MOF　nanofilm　fabricated　on　indium-tin　oxide　(ITO)　glass　possessed　enhanced　ionization　efficiency　and　size-exclusion　effect,　which　endowed　it　as　substrate　with　high　sensitivity　and　selectivity　for　serum　metabolites.　Furthermore,　the　MOF　nanofilm　with　uniform　surface　and　high　orientation　provided　high-quality　and　high-reproducibility　serum　metabolic　profiles　(SMPs)　without　any　tedious　pretreatment.　Further　analysis　of　extracted　serum　metabolic　fingerprints　could　successfully　distinguish　patients　with　CVD　from　healthy　controls　and　also　differentiate　two　major　subtypes　of　CVD.　This　work　not　only　extends　the　application　of　MOF　nanofilm　as　an　attractive　MS　probe,　but　also　provide　an　alternative　way　for　precise　diagnosis　of　CVD　in　molecular　level.　(c)　2023　Published　by　Elsevier　B.V.　on　behalf　of　Chinese　Chemical　Society　and　Institute　of　Materia　Medica,　Chinese　Academy　of　Medical　Sciences.