In this chapter, we present an up-to-date synthesis of the pathophysiology and epidemiology of skin cancer, with emphasis on both melanoma and non-melanoma entities. We review contemporary data on global incidence, geographic distribution, demographic risk profiles, and the potential contribution of diagnostic intensity and overdiagnosis to rising case numbers. We then examine UV radiation–induced DNA damage and the involvement of major oncogenic and tumor suppressor pathways (TP53, RAS/MAPK, PI3K/AKT/mTOR, CDKN2A), as well as germline susceptibility (including MC1R variants and genodermatoses) and the cutaneous microbiome. Finally, we underscore that primary prevention, early detection, and evidence-based photoprotection remain critical to reducing the global burden of skin cancer.