The　heterogeneous　single-atom　nanomaterials　(HSANs)　are　being　increasingly　embodied　in　the　field　of　sensors　due　to　their　excellent　performance　on　improving　sensitivity　based　on　the　active　centers　formed　by　the　metal-support　interaction　and　the　high　metal　utilization　efficiency.　In　this　review,　we　comprehensively　summarize　the　metal-support　interactions　during　the　process　of　HSANs　construction,　including　the　interactions　between　metal　single-atom　and　laminar　carbon-based　nanomaterials,　MOFs/MOFs-derived　nanomaterials,　metal　oxidation/sulfide　nanomaterials,　and　metal　nanomaterials.　These　metal-support　interactions　contribute　to　the　functional　characteristics　of　HSANs　due　to　the　adjustable　active　centers　such　as　M–Nx,　M–Ox,　and　M–Sx,　which　lay　good　foundation　for　sensor　applications.　Then,　the　sensors　based　on　electrocatalysis,　photocatalysis,　catalytic　colorimetry,　photoelectrochemistry　and　the　synergetic　sensing　of　active　centers　in　HSANs　are　summarized.　The　well-defined　active　centers　constructed　by　the　metal-support　interaction　are　also　highlighted　to　elucidate　the　functional　mechanism　and　structure–activity　relationship　in　sensors.　Finally,　challenges　and　opportunities　on　further　applications　of　HSANs　in　sensors　are　put　forward.　©　2022　Elsevier　B.V.