Immunotherapy has revolutionized the treatment of melanoma, but its limitations due to resistance and variable patient responses have become apparent. The microbiota, which refers to the complex ecosystem of microorganisms that inhabit the human body, has emerged as a promising area of research for its potential role in melanoma development and treatment response. Recent studies have highlighted the role of microbiota in influencing the immune system and its response to melanoma, as well as its influence on the development of immune-related adverse events associated with immunotherapy. In this article, we discuss the complex multifactorial mechanisms through which skin and gut microbiota can affect the development of melanoma including microbial metabolites, intra-tumor microbes, UV light, and the immune system. In addition, we will discuss the pre-clinical and clinical studies that have demonstrated the influence of different microbial profiles on response to immunotherapy. Additionally, we will explore the role of microbiota in the development of immune-mediated adverse events.