Since its first discovery in 1974 from the enhanced Raman spectra of pyridine molecules on roughened silver surface, surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in the ˉeld of chemistry, biology, and medicine. With the sensitivity of down to single-molecule level and the intrinsic “fingerprint" spectrum, SERS enables the ultra-sensitive, specific, selective, and multiplexing label-free analysis of a trace of molecules in aqueous biological environments, minus the interference from water, white-light or tissue auto- fluorescence background. The developments on nanofabrication technology continuously facilitate the innovation on plasmonic nanoparticles (NPs), making SERS one of the fastest developing spectroscopic and analytic techniques. Furthermore, SERS nanotags, a class of Raman-encoded and biofunctionalized plasmonic NPs, have been serving as novel optical labels to expand the SERS applications from label-free sensing to the labelled diagnostics, imaging, and intraoperative Raman image-guided surgery.…