Since May 2022, Monkeypox virus (MPXV) cases have dramatically increased worldwide. In this comprehensive review, we describe the basic characteristics, transmission routes, and susceptible individuals of MPXV as well as discuss the main causes of the current outbreak. The history, clades, genetic evolution, and transmission tendency of MPXV are depicted. Regarding viral transmission analysis in several geographical spots, we would like to point out that men who have sex with men (MSM) could play important roles in the process of transmission that eventually causes viral outbreaks. Susceptible populations at high risk of infection alert society to raise awareness on the protection of these special individuals. We also highlight that airline traveling is a driving force in causing international MPXV transmission. Further summarization of the clinical implications, the prevention of MPXV, and clinical measures of viral detection can enable the rapid diagnosis of MPXV.