In this review, we have discussed that there are several small molecule inhibitors (HNK, ABT-737, ABT-263), nanoparticles conjugated drugs (HA-SLNs-PTX), signaling antagonist (Cyclopamine, Gant61), monoclonal receptor antibodies (anti-CD20, anti-CD133, anti-ABCB5) and microRNAs (miR-200c, miR-33b) those could be used as novel therapeutic strategies for management of melanoma. This evidence concerns the gene PROM1 and melanoma.