Background <p>Refractory diseases such as cancer, Alzheimer’s disease, and rheumatoid arthritis remain difficult to treat due to drug resistance, poor targeting, and immune-related complications. Cell membrane-camouflaged nanoparticles (CCNPs) have emerged as a promising biomimetic approach, exploiting the inherent properties of natural cell membranes, including immune evasion and tissue-specific targeting.</p> Area covered <p>This review details the fabrication of CCNPs, covering cell membrane isolation methods (e.g., sonication, freeze-thaw, hypotonic lysis), nanoparticles (NPs) synthesis techniques (e.g., nanoprecipitation, emulsification), and membrane-coating techniques (e.g., co-extrusion, sonication). Applications in various refractory diseases are discussed, highlighting how CCNPs can prolong circulation, enhance immune evasion, improve tissue targeting, and minimize off-target effects.</p> Expert opinion <p>CCNPs provide a versatile and customizable platform for advanced drug delivery, combining nanotechnology with cellular mimicry. Their capacity to overcome biological barriers and selectively deliver therapeutics positions them as strong candidates for treating refractory and immune-mediated diseases. However, challenges remain in manufacturing scalability, reproducibility, and clinical-grade standardization–must be addressed to enable clinical translation. Advances in membrane engineering and regulatory-compliant production will be crucial to accelerate the translation of CCNP-based therapies into precision medicine.</p>