Cancer treatment with conventional chemotherapy drugs often faceschallenges such as poor solubility, rapid metabolism, systemic toxicity, andnon-specific distribution. Melphalan, an alkylating agent widely used inmultiple myeloma and other cancers, is clinically effective but suffers fromreduced stability and limited bioavailability. To address these drawbacks, thepresent work focused on developing melphalan-loaded niosomes as a novelnanocarrier system. The formulations were prepared using the thin filmhydration technique with cholesterol and non-ionic surfactants. They werefurther analyzed for particle size, surface charge, drug entrapmentefficiency, pH stability, compatibility studies, and in vitro release behavior.The optimized niosomal formulation exhibited nanoscale vesicles withuniform distribution, high entrapment efficiency, and stable zeta potential.FTIR analysis confirmed no significant drug–excipient interactions. Therelease profile demonstrated sustained drug release over an extended period,with kinetics indicating a diffusion-controlled mechanism. The findingssuggest that melphalan-loaded niosomes can enhance drug stability, providecontrolled delivery, reduce systemic side effects, and thereby improvetherapeutic efficacy in cancer management.