ABSTRACT Conventional approaches to live‐cell metabolomics face key barriers: Destructive methods like mass spectrometry lose spatiotemporal resolution, while noninvasive techniques are limited by phototoxicity and probe dependence. These challenges hinder the exploration of tumor metabolic reprogramming, neurodegeneration, and metabolism‐targeted therapies. Surface‐enhanced Raman scattering (SERS), with label‐free detection, single‐molecule sensitivity, and subcellular resolution, offers a promising solution. Recent advances show its capacity to monitor metabolite gradients, redox dynamics (NADH/NAD + ), and enzyme spatial distribution, as well as to visualize compartmentalized metabolism through super‐resolution imaging. This review highlights these achievements and introduces an integrated framework of molecular recognition, dynamic tracking, mechanistic insight, and translational application. Finally, we outline future opportunities combining SERS with organ‐on‐chip models and artificial intelligence, underscoring its potential in personalized medicine and in situ metabolic regulation. Overall, SERS‐based metabolomics represents a methodological breakthrough enabling cross‐scale analysis of metabolic flux in health and disease.
Chen et al. (2026) studied this question.