In recent years, hybrid cell membrane (HCM)-engineered platforms have recently emerged as powerful tools in advancing disease diagnosis and therapy, owing to their enhanced biocompatibility, intrinsic targeting capabilities, improved in vivo stability, and prolonged circulation time. These platforms are poised to revolutionize the fields of drug delivery and disease management, due to their ability to mimic the natural characteristics of biological membranes. Notably, they have significantly propelled the progress of nanomedicine by integrating cellular features, such as cell-specific targeting and immune modulation, into engineered nanosystems. This chapter provides an overview of various HCM-engineered platforms derived from different cell membrane sources and reviews the fabrication techniques for these biomimetic systems. The applications of HCM-based platforms in disease diagnosis and therapy are also discussed, focusing on conditions such as cancer, inflammation, bacterial infections, and tissue regeneration. Additionally, the chapter outlines the future prospects and current challenges in this rapidly evolving field, aiming to inspire further research across multiple disciplines and to facilitate the advancement of personalized and precision medicine.