Melanoma is one of the most aggressive skin cancers, notorious for its high multidrug resistance and low survival rate. Conventional therapies (e.g., dacarbazine, interferon-alpha-2b and interleukin-2) are limited by low response rate and demonstrate no overall survival benefit. Novel targeted therapies (e.g., vemurafenib, dabrafenib and trametinib) have higher initial response rate and clear impact on the overall survival, but relapse usually occurs within 6 to 9 months. Although immunotherapy (e.g., ipilimumab, pembrolizumab and nivolumab) can achieve long-term and durable response, rate of adverse events is extremely high. With the development of nanotechnology, the applications of nanocarriers are widely expected to change the landscape of melanoma therapy for foreseeable future. In this review, we will relate recent advances in the application of multifunctional nanocarriers for targeted drug delivery to melanoma, in melanoma nanotheranostics and combination therapy, and nanopharmaceutical associated melanoma clinical trials, followed by challenges and perspectives. From the clinical editor: The team of authors describes the current treatment regimes of malignant melanoma emphasizing the importance of achieving a better efficacy and the need to develop a better understanding of melanoma tumorigenesis.