The need for accurate point‐of‐care (POC) tools, driven by increasing demands for precise medical diagnostics and monitoring, has accelerated the evolution of biosensor technology. Integrable 2D materials‐based field‐effect transistor (2D FET) biosensors offer label‐free, rapid, and ultrasensitive detection, aligning perfectly with current biosensor trends. Given these advancements, this review focuses on the progress, challenges, and future prospects in the field of 2D FET biosensors. The distinctive physical properties of 2D materials and recent achievements in scalable synthesis are highlighted that significantly improve the manufacturing process and performance of FET biosensors. Additionally, the advancements of 2D FET biosensors are investigated in fatal disease diagnosis and screening, chronic disease management, and environmental hazards monitoring, as well as their integration in flexible electronics. Their promising capabilities shown in laboratory trials accelerate the development of prototype products, while the challenges are acknowledged, related to sensitivity, stability, and scalability that continue to impede the widespread adoption and commercialization of 2D FET biosensors. Finally, current strategies are discussed to overcome these challenges and envision future implications of 2D FET biosensors, such as their potential as smart and sustainable POC biosensors, thereby advancing human healthcare.