Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox. Initially confined to endemic regions in Central and West Africa, MPOX has recently gained global significance with outbreaks reported across multiple continents. MPXV is maintained in animal reservoirs but is increasingly transmitted from person to person, facilitated by close contact, respiratory droplets, and, in some cases, sexual transmission. Clinically, MPOX presents with fever, lymphadenopathy, and a characteristic vesiculopustular rash, though atypical manifestations have been observed in recent outbreaks, complicating diagnosis. Laboratory confirmation relies on molecular testing, while differential diagnosis must consider varicella, herpes, and other vesicular illnesses. Therapeutic options remain limited; supportive care is the cornerstone of management, but antivirals such as tecovirimat and brincidofovir, as well as smallpox vaccines, have shown efficacy in mitigating disease severity and preventing infection. The unprecedented global outbreak has underscored the importance of surveillance, rapid diagnostics, and coordinated public health responses to contain transmission. This review provides an overview of epidemiology, virology, clinical manifestations, modes of transmission, available diagnostics, and prophylactic and therapeutic strategies against MPOX. We also discuss the role of animal reservoirs, viral evolution, and human-to-human transmission in shaping the dynamics of recent MPOX outbreaks. By summarizing the latest evidence, this review aims to inform clinicians, researchers, and policymakers about key aspects of MPOX biology, clinical management, and prevention, while identifying gaps that warrant future investigation for the control of this and potentially other emerging zoonotic-related pathogens with an impact on human health.