Various methods for creating SERS nanosubstrates are shown here. (A) Schematic showing asymmetric nanoporous gold nanoparticles, which form nanoporous gold bowls, and through electrochemical‐SERS, able to produce enantiospecific molecular fingerprints for a label‐free approach to chiral differentiation (adapted with permission from Ref. [45]. Copyright 2021 American Chemical Society). (B) High‐magnification SEM image of a nanoporous gold bowl (adapted with permission from Ref. [45]). (C) Schematic illustration showing the synthesis of a bimetallic nanoparticle with an embedded internal standard for quantitative detection. The nanoparticle utilizes a gold core, 4‐Mpy as the embedded Raman probe and a silver shell for both protection and enhancement (Au@4‐Mpy@AgNP) (reprinted with permission from Ref. [70]. Copyright 2021 Royal Society of Chemistry). (D) TEM image of a Au@4‐Mpy@AgNP (reprinted with permission from Ref. [70]). (E) Schematic representation for the preparation of the dual DTNB‐modified gold‐shell silica‐core nanoparticles (SiO2/Au NPs) for the quantitative detection of E. coli (adapted with permission from Ref. [232]. Copyright 2020 Shi, Xu, Xiao, Zhou, Wang, Wang and Gu)