The 2022 multi-national outbreak of mpox (previously known as monkeypox) has shaken the global community, which was just beginning to recover from the aftermath of the COVID-19 pandemic. This outbreak has occurred in various non-African regions, accompanied by reports of human-to-human transmission. The present manuscript provides a comprehensive review of the causative agent, epidemiology of mpox in both animal and human populations, modes of transmission, clinical manifestations, diagnostic approaches, as well as strategies for disease control and prevention. Notably, the World Health Organization has recently recommended the use of the term “mpox” instead of “monkeypox” to avoid any potential social stigmas associated with the previous nomenclature, which is reflected in the terminology used throughout this work.