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Monkeypox (Mpox), an uncommon zoonotic Orthopoxvirus, is commonly manifested by blisters on the skin and has a mortality rate of approximately 0-10%. Approximately two decades after the cessation of global smallpox vaccination, the number of confirmed cases of Mpox has been growing, making it the most common Orthopoxvirus infection. Therefore, in this narrative review, we aimed to shed light on recent advancements in the pathophysiology, transmission routes, epidemiology, manifestations, diagnosis, prevention, and treatment of Mpox, as well as the application of artificial intelligence (AI) methods for predicting this disease. The clinical manifestations of Mpox, including the onset of symptoms and dermatologic characteristics, are similar to those of the infamous smallpox, but Mpox is clinically milder. Notably, a key difference between smallpox and Mpox is the high prevalence of lymphadenopathy. Human-to-human, animal-to-human, and animal-to-animal transmission are the three main pathways of Mpox spread that must be considered for effective prevention, particularly during outbreaks. PCR testing, as the preferred method for diagnosing Mpox infection, can enhance early detection of new cases and thereby improve infection control measures. JYNNEOS and ACAM2000 are among the vaccines most commonly recommended for the prevention of Mpox. Brincidofovir, Cidofovir, and Tecovirimat are the primary treatments for Mpox cases. Similar to other viral infections, the best approach to managing Mpox is prevention. This can, in part, be achieved through measures such as reducing contact with individuals displaying symptoms, maintaining personal safety, and adhering to practices commonly used to prevent sexually transmitted infections.