Simple SummaryMelanoma is a dreadful type of skin cancer with a poor response to therapy. Senescent cells have been found to accumulate with age and may contribute to the occurrence and development of melanoma. This review aims to provide an overview of skin aging and melanoma, including the molecular mechanisms, microenvironmental factors, and therapeutic strategies. In addition, some potential common targets between melanoma and cell senescence will be also discussed.AbstractMelanoma is a malignant skin tumor that originates from melanocytes. The pathogenesis of melanoma involves a complex interaction that occurs between environmental factors, ultraviolet (UV)-light damage, and genetic alterations. UV light is the primary driver of the skin aging process and development of melanoma, which can induce reactive oxygen species (ROS) production and the presence of DNA damage in the cells, and results in cell senescence. As cellular senescence plays an important role in the relationship that exists between the skin aging process and the development of melanoma, the present study provides insight into the literature concerning the topic at present and discusses the relationship between skin aging and melanoma, including the mechanisms of cellular senescence that drive melanoma progression, the microenvironment in relation to skin aging and melanoma factors, and the therapeutics concerning melanoma. This review focuses on defining the role of cellular senescence in the process of melanoma carcinogenesis and discusses the targeting of senescent cells through therapeutic approaches, highlighting the areas that require more extensive research in the field.