Mpox, formerly known as monkeypox, is caused by the Monkeypox virus (MPXV), a large double stranded DNA virus belonging to the Orthopoxvirus genus. In recent years, the disease has gained increasing global attention following a series of outbreaks that extended beyond its historically endemic regions in Central and West Africa. These outbreaks have highlighted the evolving epidemiology of the virus, the importance of timely public health responses, and the critical role of vaccination in outbreak control. This chapter explores the changing epidemiology and mpox transmission routes, reviews available vaccines and vaccination strategies, addresses ongoing challenges, and highlights remaining knowledge gaps and future perspectives on mpox vaccination.