In view of basic science, to understand biological systems increasingly depends on our ability to dynamically and quantitatively measure the molecular processes with high sensitivity, speed, flexibility, multiplexity, throughput, and reproducibility, usually within the context of a complex biological and chemical mixture of a tiny amount. Raman scattering, first demonstrated by C. V. Raman in 1928, occurs because of the inelastic scattering of light from molecules or atoms. Then, in the mid-1970s, the explosion of activity in the field of surface-enhanced Raman scattering (SERS) started. The underlying phenomena exploited for SERS-sensing applications are based on the interaction of light and matter at nanoscale surfaces. When the incoming electromagnetic radiation is coupled to the localized excitation of conductor electrons at the dielectric–metal interface of a metal NP, quantitative spectral data as a function of local environmental changes over time can be gathered.