This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery systems. Metal-organic frameworks (MOFs), particularly zeolitic imidazolate framework-8 (ZIF-8), are widely used due to their robust stability in aqueous environments and pH-responsive properties. ZIF-8's biomimetic nature enhances its biocompatibility and targeting capabilities, making it an attractive candidate for drug delivery. The review discusses various synthesis methods of ZIF-8, including the multiple emulsification-solvent evaporation method, solvent evaporation seeding coupled microwave-assisted heating method, direct solvent-free synthesis, and one-pot methods. Surface modifications, such as coating with PEG, hyaluronic acid (HA), chitosan, and polyvinylpyrrolidone (PVP), are crucial for improving stability, reducing immune reactions, and enhancing drug release control. The use of biomimetic materials, such as erythrocyte, cancer cell, neutrophil, stem cell, and extracellular vesicle membranes, further enhances the biocompatibility, stability, and targeted delivery of ZIF-8 nanoparticles. These modifications enable specific targeting, prolonged circulation time, and enhanced therapeutic efficacy in various diseases, including cancer, osteosarcoma, and antimicrobial therapy. The review highlights the potential of biomimetic ZIF-8 nanoparticles in overcoming limitations of conventional drug delivery systems and their promising applications in biomedical research and clinical practice.This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery systems. Metal-organic frameworks (MOFs), particularly zeolitic imidazolate framework-8 (ZIF-8), are widely used due to their robust stability in aqueous environments and pH-responsive properties. ZIF-8's biomimetic nature enhances its biocompatibility and targeting capabilities, making it an attractive candidate for drug delivery. The review discusses various synthesis methods of ZIF-8, including the multiple emulsification-solvent evaporation method, solvent evaporation seeding coupled microwave-assisted heating method, direct solvent-free synthesis, and one-pot methods. Surface modifications, such as coating with PEG, hyaluronic acid (HA), chitosan, and polyvinylpyrrolidone (PVP), are crucial for improving stability, reducing immune reactions, and enhancing drug release control. The use of biomimetic materials, such as erythrocyte, cancer cell, neutrophil, stem cell, and extracellular vesicle membranes, further enhances the biocompatibility, stability, and targeted delivery of ZIF-8 nanoparticles. These modifications enable specific targeting, prolonged circulation time, and enhanced therapeutic efficacy in various diseases, including cancer, osteosarcoma, and antimicrobial therapy. The review highlights the potential of biomimetic ZIF-8 nanoparticles in overcoming limitations of conventional drug delivery systems and their promising applications in biomedical research and clinical practice.