Surface-assisted　laser　desorption/ionization　mass　spectrometry　(SALDI-MS)　has　been　regarded　as　one　of　the　prominent　techniques　in　small　molecule　analysis,　which　employs　nanostructured　materials　as　substrates　to　replace　conventional　organic　matrices　for　laser　absorption　and　analyte　desorption/ionization.　The　rational　design　and　development　of　nanostructured　substrates,　particularly　metal-organic　frameworks　(MOFs)　and　covalent-organic　frameworks　(COFs),　are　crucial　for　enhancing　SALDI-MS　performance.　This　review　aims　to　cover　the　latest　developments　(within　5　years)　in　nanostructured　substrates　in　SALDI-MS,　including　carbon-　and　silicon-based　materials,　metals　and　their　oxide　materials,　MOFs,　COFs,　and　other　materials.　The　key　design　parameters　that　affect　the　SALDI-MS　efficiency　of　these　nanomaterials　in　small　molecule　analysis,　such　as　pore　size,　surface　area,　and　functional　groups,　are　also　discussed.　Furthermore,　the　applications　of　SALDI-MS　in　various　fields　are　reviewed.　Lastly,　the　challenges　and　prospects　for　future　research　on　the　design　of　nano-　structured　substrates　for　SALDI-MS　in　small　molecule　analysis　are　discussed.