Monkeypox (mpox) is a viral infection closely related to smallpox, manifesting as a milder febrile rash in affected individuals. Over the past two decades, the incidence of mpox has surged, possibly linked to a declining immunity against the smallpox vaccine worldwide. Recent outbreaks of mpox in multiple countries have sparked concerns regarding altered transmission patterns and the potential for a global menace. In this article, we present a multidimensional review encompassing the latest scientific discoveries, illuminating the intricate structure of the human mpox virus. Key findings include advancements in understanding the virus’s molecular mechanisms, which highlight its genetic adaptability and potential for zoonotic spillover. Diagnostic innovations, such as improved molecular assays, have enhanced detection accuracy, while novel therapeutic strategies, including antiviral drugs and vaccines, show promise in mitigating outbreaks. Our conclusions emphasize the importance of robust surveillance systems, vaccination programs, and rapid response strategies to curb mpox’s spread. Future recommendations include strengthening global collaboration for zoonotic disease surveillance, advancing the research on host–pathogen interactions, and developing next-generation therapeutics to address this emerging public health threat effectively.