Monkeypox virus, a member of the Orthopoxvirus genus, has emerged as a significant public health concern, primarily within Central and West Africa. This comprehensive review navigates the complex landscape of Monkeypox, delving into its transmission, clinical presentation, diagnosis, treatment, epidemiology, prevention, and on-going research challenges. The review begins with an exploration of the virus's origins, virology, and mechanisms of transmission. It examines the diverse clinical manifestations of Monkeypox, ranging from mild flu-like symptoms to severe cases with extensive skin lesions, highlighting the importance of early diagnosis and differential diagnosis from similar diseases. Epidemiologically, Monkeypox exhibits sporadic outbreaks in endemic regions, with the risk of international spread, necessitating robust surveillance and preparedness efforts. Global collaboration and vaccination strategies are essential in controlling outbreaks and preventing widespread dissemination. Lastly, the article underscores the significance of on-going research in understanding the virus's genetic diversity, host factors influencing susceptibility, and the development of effective Monkeypox vaccines and therapies. The need for a One Health approach, recognizing the interconnectedness of human, animal, and environmental health, is paramount in addressing this emerging infectious disease. In conclusion, this review encapsulates the multifaceted nature of Monkeypox and emphasizes the imperative of continued research, global vigilance, and preparedness to safeguard public health against emerging threats in an interconnected world.