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This chapter will thoroughly examine how the landscape of skin cancer therapeutics is changing with a particular focus on the fact that nanotechnology has resulted in a transformative advancement in drug delivery systems. It starts by providing a summary of the epidemiology of skin cancer, and the treatment difficulties that are associated with conventional modalities, including surgery, radiotherapy, and topical chemotherapy, and their shortcomings. The wide variety of nanocarriers, including lipid-based systems, polymeric nanoparticles, micelles, dendrimers, and inorganic platforms like gold nanoparticles and quantum dots, are then discussed along with their physicochemical properties, the mechanism of improved drug solubility, stability, bioavailability, and targeted activity. The hybrid and stimuli-sensitive delivery systems that are intended to be delivered on the site of action in response to internal (pH, redox, enzyme) or exterior (light, temperature, magnetic field) stimuli receive particular attention. The efforts to optimize therapeutic utility and reduce toxicity in the off-target tissues through enhanced permeability and retention (EPR) impact and ligand-based targeting are among the passive and active tumor targeting mechanisms that are taken into consideration.The chapter ends with a discussion on the recent research, combination therapies, theranostics, and future on clinical translation of nanotechnology-based methods in managing skin cancer.