Metal–organic framework (MOF)-based surface-enhanced Raman scattering (SERS) sensors have emerged as a versatile platform for high-sensitivity and selective detection in agricultural, environmental, and biomedical applications. By integrating plasmonic nanostructures with tunable MOF architectures, these hybrid systems combine ultrahigh signal enhancement with molecular recognition, analyte preconcentration, and controlled hotspot distribution. This review provides a comprehensive overview of the fundamental principles underpinning MOF–SERS performance, including EM and chemical enhancement mechanisms, and highlights strategies for substrate design, such as metal–MOF composites, plasmon-free frameworks, ligand functionalization, and hierarchical or core–shell architectures. We further examine their applications in environmental monitoring, pesticide and contaminant detection, pathogen identification, biomarker analysis, and theranostics, emphasizing real-sample performance, molecular selectivity, and emerging integration with portable Raman devices and AI-assisted data analysis. Despite notable advances, challenges remain in reproducibility, quantitative reliability, matrix interference, scalability, and biocompatibility. Future developments are likely to focus on rational MOF design, sustainable fabrication, intelligent spectral interpretation, and multifunctional integration to enable robust, field-deployable sensors. Overall, MOF-based SERS platforms represent a promising next-generation analytical tool poised to bridge laboratory innovation and practical, real-world applications.
Kidanemariam et al. (Mon,) studied this question.