Interfacial Chemistry in SERS: Mechanisms, Controls, and Materials

Surface-enhanced Raman scattering (SERS) is a powerful spectroscopic tool for molecular analysis, in which molecular-surface interactions, adsorption energetics, and electronic coupling govern activation, selectivity, and sensitivity. Despite this, SERS interpretation and design have been dominated by electromagnetic field enhancement, leaving chemical enhancement and interfacial understanding limited and fragmented, with surface chemistry often treated as a black box in which ligands and coatings are applied empirically with little mechanistic insight. In this perspective, we reemphasize SERS as an interfacial chemical phenomenon, viewing SERS substrates as chemically active interfaces with tunable energetic, geometric, and electronic states. We introduce a SERS interfacial chemical phase diagram that organizes substrate-analyte interactions across these dimensions, enabling mechanistic understanding, rational control, and predictive design. Furthermore, we evaluate emerging strategies for actively tuning interfacial states through chemical functionalization, porous and compartmentalized materials, adaptive architectures, and hybrid systems, and highlight opportunities to integrate computation, standardized interfacial metadata, and interpretable machine learning to advance SERS into a chemically designable and predictive platform for targeted analysis and operando studies.