Cell surface engineering strategies aim to functionalize living cells and cell membrane-based platforms, such as membrane vesicles and membrane-coated nanoparticles, by modifying their membranes. These modifications enhance targeted homing, tissue penetration, selective accumulation, drug-loading efficiency, real-time monitoring, precise antigen presentation, and immune modulation for disease-specific therapies. Various ligands and biomolecules, such as peptides, biopolymers, nanoparticles, nucleic acids, and bioactive proteins, have been attached to membrane-based platforms using diverse methods. Biomaterial-based cell membrane engineering strategies, including covalent coupling, hydrophobic interaction, electrostatic interaction, membrane fusion, and metabolic glycoengineering, along with integrated approaches, have been introduced to enhance the functionality of cell membrane-based platforms. Biomaterial-based strategies are increasingly utilized because of their low cost, low toxicity, broad applications, and ease of engineering compared to genetic engineering-based strategies. These methods have been extensively utilized in cancer therapy, precision drug delivery, tissue engineering and other biomedical applications. This chapter describes cell membrane features and the need for membrane engineering to enhance biomedical applications. It emphasizes chemically driven engineering strategies using biomaterials, highlighting their potential to improve outcomes for living cells and membrane-based platforms in biomedical applications, while also discussing the ongoing challenges of these strategies.