：Engineered Cell Membrane (ECM) has emerged as a promising strategy for the treatment of both tumor and non-tumor diseases. By modifying the surface molecules of cell membranes through physical, chemical, and biological approaches, ECM technology can enhance targeted recognition, promote phagocytosis, modulate immune responses, and improve bioimaging, while maintaining the inherent properties of natural cell membrane (NCM). However, few studies have provided a comprehensive overview of the modified molecular characteristics, underlying mechanisms, and their applications in both benign and malignant diseases. In this review, we summarize the key molecules commonly incorporated into ECM (such as immunosuppressive molecules, immune-promoting molecules, targeted recognition molecules, and permeability-enhancing molecules), along with their underlying mechanisms. We also discuss current methodologies for ECM and explore its applications in the treatment of tumor and non-tumor diseases. Finally, we address the challenges and future prospects of ECM technology for clinical translation.