Abstract <p>The rapid detection and handling of diseases continue to be a priority, improving patient care and individualized treatment. Expensive equipment, the need for expert operators, and extended analytical processes often limit traditional diagnostic methods. Sensor-based approaches for efficient exhaled breath analysis offer a favorable non-invasive alternative. Patients can easily provide exhaled breath, which serves as a nearly inexhaustible diagnostic sample with minimal discomfort. “Breathomics” is an emerging research realm that deeply investigates the metabolomic constitution of exhaled breath, offering information about several (patho)physiological processes. Breathomics reveals unusual products of metabolism by analyzing volatile organic compounds (VOCs) in exhaled breath. Incorporating artificial intelligence (AI), machine learning (ML), and the Internet of Things into breathomics can improve the identification of patterns in breath biomarkers, data analysis, and real-time disease diagnosis. Metal-organic frameworks (MOFs) are promising materials for the production of high-performance gas sensors. They possess porous architectures, substantial surface areas, unique compositions, and functional linkers. The implementation of MOFs as gas-sensitive elements may alter their physical and/or chemical properties. This effect is noticeable during the adsorption and desorption of gases. This review discusses emerging advancements in precise breath-based disease diagnosis using MOFs in various technologies, including electrochemical, chemiresistive, quartz crystal microbalance, and surface-enhanced Raman spectroscopy systems.</p> Graphical abstract <p></p>