The modern healthcare system strives to provide patients with more comfortable and less invasive experiences, focusing on noninvasive and painless diagnostic and treatment methods. A key priority is the early diagnosis of life-threatening diseases, which can significantly improve patient outcomes by enabling treatment at earlier stages. While most patients must undergo diagnostic procedures before beginning treatment, many existing methods are invasive, time-consuming, and inconvenient. To address these challenges, electrochemical-based wearable and point-of-care (PoC) sensing devices have emerged, playing a crucial role in the noninvasive, continuous, periodic, and remote monitoring of key biomarkers. Due to their numerous advantages, several wearable and PoC devices have been developed. In this focused review, we explore the advancements in metal–organic frameworks (MOFs)-based wearable and PoC devices. MOFs are porous crystalline materials that are cost-effective, biocompatible, and can be synthesized sustainably on a large scale, making them promising candidates for sensor development. However, research on MOF-based wearable and PoC sensors remains limited, and no comprehensive review has yet to synthesize the existing knowledge in this area. This review aims to fill that gap by emphasizing the design of materials, fabrication methodologies, sensing mechanisms, device construction, and real-world applicability of these sensors. Additionally, we underscore the importance and potential of MOF-based wearable and PoC sensors for advancing healthcare technologies. In conclusion, this review sheds light on the current state of the art, the challenges faced, and the opportunities ahead in MOF-based wearable and PoC sensing technologies.