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Surface-enhanced Raman spectroscopy (SERS) has revolutionized molecular detection by exploiting the phenomenon of localized surface plasmon resonance in noble metal nanostructures, achieving signal enhancement factors of up to 10¹⁴. This transformative technology reshapes biomedical practice through two fundamental mechanisms: nanoscale “hotspot” electromagnetic field amplification and chemical charge transfer effects. This review focuses on the cutting-edge applications of SERS in biochemical analysis. It begins by dissecting the nuts and bolts of engineered SERS tags: (1) plasmonic nanoparticles as enhancers; (2) Raman reporter molecules for fingerprint identification; (3) protective shells; and (4) selective functionalization for biomolecules, as well as how these molecules are designed, optimized, and fine-tuned for precision. Specifically, the review emphasizes the clinical potential of SERS tags: (1) tumor biomarker detection and in vitro diagnostics; (2) bioimaging; (3) tumor therapy; and (4) AI-assisted tumor diagnosis and treatment. Finally, we provide a forward-looking perspective on the use of SERS in biomedicine, such as multimodal integration, standardized detection protocols, AI-based on-site spectral analysis, and large-scale clinical applications.
