Monkeypox (MPX) is a double-stranded DNA virus belonging to the Poxviridae family. It can be transmitted through direct contact with infected skin lesions, body fluids, air droplets, sexual contact, and/or contaminated fomites. MPX has a broad range of clinical findings and complications, ranging from mild symptoms to severe fatal complications. To elucidate MPX and its possible resurgence. This review discusses the epidemiology, clinical findings, diagnosis, prevention, and future challenges associated with MPX. A resurgence of MPX has been reported in many non-endemic countries that do not have any relation to the importation of animals or travel. Many transformations occur in MPX, resulting in its ability to infect and spread among humans. Based on its very high rates of spread and variable findings, great caution should be taken worldwide to gauge the next resurgence.