The skin microbiome plays a crucial role in maintaining skin health, defending the body against harmful pathogens, and interacting with melanoma. The composition of the skin microbiome can be affected by factors like age, gender, ethnicity, lifestyle, diet, and UV exposure. Certain bacteria like Staphylococcus and Veillonella are important for wound healing, while Cutibacterium acnes can play a role in dermatoses. UV radiation alters the skin microbiome, originates a "UV-resistome" and can lead to skin cancer initiation. Specifically, Staphylococcus epidermidis has shown protective effects against skin cancer, whereas Cutibacterium acnes can induce apoptosis in melanocytes postirradiation. The microbiome also interacts with melanoma treatment, affecting responses to immune checkpoint inhibitors. Strategies like bacteriotherapy, involving the manipulation of the gut microbiome but also the skin microbiome (with the gut-skin axis or through topical treatment) could improve treatment outcomes and show promise in melanoma therapy. Understanding the complex interplay between the skin microbiome, UV exposure, and melanoma development is crucial for developing personalized therapeutic approaches. Investigation into the skin microbiome and its potential role in melanoma progression continues to be an exciting area of research with implications for future therapeutic interventions.