Precision　cancer　medicine　necessitates　a　personalized　treatment　plan　for　each　individual　patient.　Given　cancer’s　heterogeneity　and　dynamic　nature,　the　plot　of　patient-specific　signatures　composed　of　multiple　cancer　circulating　biomarkers　is　useful　to　reveal　the　complete　tumor　landscape　for　guiding　precision　medicine.　As　an　emerging　new　technology,　surface-enhanced　Raman　scattering　(SERS)　shows　the　intrinsic　advantage　of　performing　multiplexed　detection　with　the　extremely　narrow　Raman　spectral　line　widths.　In　this　review,　we　first　discuss　the　design　principle　of　SERS　nanotags　to　enable　the　detection　of　multiple　circulating　biomarkers,　highlighting　the　important　roles　of　plasmonic　nanostructures　and　triple　bond-modulated　Raman　reporters.　Following　this,　we　detail　the　use　of　isotropic　and　anisotropic　nanostructures　as　SERS　enhancement　substrates　for　amplifying　Raman　signals　in　multi-biomarker　detection.　Furthermore,　we　present　the　triple　bond-modulated　molecules　as　Raman　reporters　in　SERS　nanotags　to　expand　the　multiplexing　capability　for　biomarker　measurements.　Finally,　we　offer　critical　insights　into　the　challenges　and　perspectives　of　SERS　nanotags　for　cancer　diagnosis,　particularly　from　the　aspect　of　future　clinical　transition.　It　is　expected　that　this　review　can　facilitate　the　design　of　more　functional　SERS　nanotags　with　high　sensitivity　and　multiplexing　capability　to　assist　early　and　accurate　cancer　screening.　We　also　believe　our　review　will　be　of　interest　in　the　fields　of　molecular　imaging,　biomedicine,　and　analytical　chemistry.　©　2023　by　the　authors.