Metal-Organic Frameworks (MOFs) are being explored for enhancing Surface-Enhanced Raman Spectroscopy (SERS) for the detection of Volatile Organic Compounds (VOCs). VOCs are harmful environmental pollutants and are relevant in various fields, including disease diagnostics and food quality assessment. Traditional methods like Gas Chromatography (GC) are effective but limited in portability and sample preparation. SERS offers a rapid, sensitive, and specific detection method but requires efficient analyte docking on metallic surfaces. MOFs, with their porous structures and chemical versatility, can pre-concentrate VOCs and improve SERS performance. This review discusses recent developments in MOF-based SERS substrates, focusing on design principles for optimal analytical performance. It covers VOC detection in industrial and environmental monitoring, medical diagnostics through VOC biomarkers, and emerging applications in aroma and flavor profiling. MOFs are particularly useful for VOC pre-concentration due to their high surface area and tunable pore structures. The integration of MOFs with plasmonic nanostructures enhances SERS performance by enabling selective trapping of VOCs at the SERS-active surface. The review highlights the importance of optimizing MOF and plasmonic components for efficient SERS detection. MOFs offer advantages such as tunable optical properties, chemical versatility, and the ability to enhance both electromagnetic and chemical mechanisms in SERS. The review also discusses the performance characteristics of MOF-based SERS detection formats, including enhancement factors, detection times, and analytical practices. The analysis of VOCs is crucial for environmental and industrial monitoring, as VOCs are major sources of air pollution and have significant health impacts. MOF-based SERS provides a promising solution for rapid, sensitive, and selective VOC detection, with potential applications in various fields. The review emphasizes the need for systematic design and analysis of MOF-based SERS substrates to maximize performance and ensure reliable detection of VOCs.Metal-Organic Frameworks (MOFs) are being explored for enhancing Surface-Enhanced Raman Spectroscopy (SERS) for the detection of Volatile Organic Compounds (VOCs). VOCs are harmful environmental pollutants and are relevant in various fields, including disease diagnostics and food quality assessment. Traditional methods like Gas Chromatography (GC) are effective but limited in portability and sample preparation. SERS offers a rapid, sensitive, and specific detection method but requires efficient analyte docking on metallic surfaces. MOFs, with their porous structures and chemical versatility, can pre-concentrate VOCs and improve SERS performance. This review discusses recent developments in MOF-based SERS substrates, focusing on design principles for optimal analytical performance. It covers VOC detection in industrial and environmental monitoring, medical diagnostics through VOC biomarkers, and emerging applications in aroma and flavor profiling. MOFs are particularly useful for VOC pre-concentration due to their high surface area and tunable pore structures. The integration of MOFs with plasmonic nanostructures enhances SERS performance by enabling selective trapping of VOCs at the SERS-active surface. The review highlights the importance of optimizing MOF and plasmonic components for efficient SERS detection. MOFs offer advantages such as tunable optical properties, chemical versatility, and the ability to enhance both electromagnetic and chemical mechanisms in SERS. The review also discusses the performance characteristics of MOF-based SERS detection formats, including enhancement factors, detection times, and analytical practices. The analysis of VOCs is crucial for environmental and industrial monitoring, as VOCs are major sources of air pollution and have significant health impacts. MOF-based SERS provides a promising solution for rapid, sensitive, and selective VOC detection, with potential applications in various fields. The review emphasizes the need for systematic design and analysis of MOF-based SERS substrates to maximize performance and ensure reliable detection of VOCs.