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Skin cancer is considered one of the most significant malignancies worldwide, arising primarily from epidermal keratinocytes or melanocytes and influenced by genetic, environmental, and lifestyle factors. Conventional therapies, including chemical treatments, chemotherapy, radiotherapy, and antibody immunotherapy, though most effective in the early stages, often present significant limitations including such as systemic toxicity, recurrence, drug resistance, and cosmetic or psychological impacts. In recent years, nanotechnology has emerged as a promising strategy to overcome these challenges by enabling targeted, efficient, and minimally invasive therapeutic approaches. Nanoparticles, with their tunable size, surface properties, and biocompatibility, facilitate site-specific drug delivery, improve solubility of poorly soluble agents, and prolong drug circulation time while minimizing off-target effects. Diverse nanocarrier systems-liposomes, niosomes, dendrimers, micelles, nanospheres, nanoemulsions, and metallic nanoparticles-have been investigated for skin cancer therapy, offering improved penetration across the stratum corneum, controlled release, and enhanced drug retention. Functional modifications such as PEGylation and ligand attachment further optimize stability, immune evasion, and receptor-mediated targeting. Moreover, nanotechnology integrates diagnostic and therapeutic potential through theranostic applications, enabling simultaneous imaging, monitoring, and treatment of skin malignancies. Despite regulatory and translational challenges, advancements in nanoparticle-based therapeutics represent a paradigm shift in precision dermatologic oncology, offering safer, more effective, and patient-friendly interventions. This chapter highlights recent progress, clinical perspectives, and future directions in nanotechnology-enabled skin cancer therapies.