Recent cases of monkeypox (MPX), a zoonotic illness caused by monkeypox virus (MPXV), outside of Africa have prompted international public health concerns. The emergence, re-emergence, and global dispersion of zoonoses are profoundly impacted by a wide variety of causes, including but not limited to climate change, urbanization, animal migration, quick means of travel and tourism, vector biology, anthropogenic influences, and natural factors. Human MPX was first identified in the Democratic Republic of the Congo (DRC) in 1970, and since then it has spread throughout Africa, particularly to West and Central Africa, with some instances even emerging outside of Africa. Since the 1970s, there has been an increasing trend in the occurrence of human MPX, with the DRC seeing the largest increase. The median age at first presentation has increased from 4 years in the 1970s to 21 years in the current time. The total fatality rate was 8.7%, although there was a significant variation between clades: Central African (10.6%) and West African (3.6%). Since 2003, sporadic outbreaks have occurred outside of Africa due to imports and travel-related dissemination. Risky practices that could lead to contracting MPX include having contact with infected animals or people. There is still much to learn about MPXV, such as the reason for the sudden increase in cases while travel links from endemic countries have not yet been established profoundly, identity the natural reservoir animal(s), make advances in diagnostics, increase surveillance and monitoring, carry out in-depth epidemiological investigations, genome sequencing and phylogenetic analysis, explore the reasons for the changing epidemiology and evolving nature of the virus, its ecological niche, and the discovery of effective treatment and management of MPX. This l mini-review aims to reveal an increase in the number of reported cases of MPX worldwide, with the highest concentration in the DRC, as well as its spread to other countries and a shift in the median age of patients from infants to teenagers and young adults highlighting from older years to current 2022 MPX outbreaks. Some cross-protection against MPX was provided by smallpox vaccination, suggesting that its discontinuation may have contributed to an increase in human-to-human transmission. The disease’s worldwide significance is underscored by the fact that it has spread beyond Africa. As the epidemiology of this resurging disease is constantly shifting, surveillance and detection programs are crucial to keeping up with it.