Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 articles were selected for review. Qualitative analysis revealed that nanoscale systems demonstrate significant antineoplastic and anti-metastasis properties: increased drug bioavailability, reduced toxicity, enhanced permeability and retention effect, as well as tumor growth inhibition, among others. Nanoformulations for skin cancers have largely lagged behind those tested in other cancers-several of which have commercialized formulae. However, emerging evidence has indicated a powerful role for these carriers in targeting primary and metastatic skin cancers.