This review discusses the application of Metal–Organic Frameworks (MOFs) in Surface-Enhanced Raman Spectroscopy (SERS) for the analysis of Volatile Organic Compounds (VOCs). VOCs are significant environmental pollutants and have applications in early disease diagnostics and food quality assessment. SERS offers rapid and portable detection, but the need for efficient analyte docking limits its applicability. MOFs, with their chemical and structural versatility, can pre-concentrate low molecular weight species like VOCs through their ordered porous structure. The review highlights recent trends in MOF-based SERS substrates, focusing on design rules to maximize analytical performance. It also discusses the detection of harmful VOCs in industrial and environmental monitoring, the analysis of VOC biomarkers for medical diagnosis, and potential applications in aroma and flavor profiling. The combination of MOFs with SERS provides a promising platform for sensitive and specific VOC detection, with MOFs enhancing the electromagnetic and chemical mechanisms contributing to the SERS signal. The review covers the characteristics of SERS substrates with MOFs, including the optimization of thickness, plasmonic performance, and the interplay between MOF and metallic nanostructures. It also presents performance characteristics of MOF-based SERS detection formats, emphasizing the importance of instrumental parameters, substrate design, and analyte properties. Finally, the review explores the environmental and industrial monitoring applications of MOF-based SERS, highlighting the detection of harmful VOCs such as nitrobenzene and naphthalene.This review discusses the application of Metal–Organic Frameworks (MOFs) in Surface-Enhanced Raman Spectroscopy (SERS) for the analysis of Volatile Organic Compounds (VOCs). VOCs are significant environmental pollutants and have applications in early disease diagnostics and food quality assessment. SERS offers rapid and portable detection, but the need for efficient analyte docking limits its applicability. MOFs, with their chemical and structural versatility, can pre-concentrate low molecular weight species like VOCs through their ordered porous structure. The review highlights recent trends in MOF-based SERS substrates, focusing on design rules to maximize analytical performance. It also discusses the detection of harmful VOCs in industrial and environmental monitoring, the analysis of VOC biomarkers for medical diagnosis, and potential applications in aroma and flavor profiling. The combination of MOFs with SERS provides a promising platform for sensitive and specific VOC detection, with MOFs enhancing the electromagnetic and chemical mechanisms contributing to the SERS signal. The review covers the characteristics of SERS substrates with MOFs, including the optimization of thickness, plasmonic performance, and the interplay between MOF and metallic nanostructures. It also presents performance characteristics of MOF-based SERS detection formats, emphasizing the importance of instrumental parameters, substrate design, and analyte properties. Finally, the review explores the environmental and industrial monitoring applications of MOF-based SERS, highlighting the detection of harmful VOCs such as nitrobenzene and naphthalene.