BACKGROUND: Monkeypox (Mpox), a zoonotic viral disease caused by the Mpox virus (MPOXV), was first identified in 1958 and remained largely confined to Central and West Africa for decades. While it usually exhibited limited international transmission, recent outbreaks, including in the USA in 2003 and globally in 2024, highlight significant epidemiological shifts. We aimed to systematically evaluate the evolution of Mpox from 1958 to 2024, focussing on its epidemiology, viral evolution, and public health responses. METHODS: We conducted a systematic review using data from global health reports, surveillance databases, and published literature. The analysis covered key outbreaks, transmission patterns, geographic distribution, public health responses, and the roles of viral mutations and vaccination in disease management. RESULTS: The 2022 Mpox outbreak, declared a Public Health Emergency of International Concern by the World Health Organization (WHO), was characterised by an unprecedented international spread of the virus. By July 2024, a total of 102 997 confirmed cases and 223 deaths were reported across 121 countries. Two distinct viral clades were identified: Central African (clade I) and West African (clade II), with the latter being the primary agent of global transmission. Research on Mpox has highlighted the protective effects of smallpox vaccination and emerging risk factors such as human-animal interactions and international travel. CONCLUSIONS: Mpox has evolved from a regionally contained zoonotic disease to a global public health challenge. Enhanced surveillance, international collaboration, and targeted interventions in non-endemic regions are critical for mitigating future outbreaks and managing ongoing epidemiological changes.