Based on recent multiregional epidemiological investigations of Monkeypox (MPX), on 24 July 2022, the World Health Organization declared it a global public health threat. Retrospectively MPX was an ignored zoonotic endemic infection to tropical rainforest regions of Western and Central African rural communities until a worldwide epidemic in May 2022 verified the potential threat of monkeypox virus (MPXV) to be propagated across the contemporary world via transnational tourism and animal movements. During 2018–2022, different cases of MPX diagnosed in Nigerian travelers have been documented in Israel, the United Kingdom, Singapore, and the United States. More recently, on 27 September 2022, 66,000 MPX cases have been confirmed in more than 100 non-endemic countries, with fluctuating epidemiological footprinting from retrospective epidemics. Particular disease-associated risk factors fluctuate among different epidemics. The unpredicted appearance of MPX in non-endemic regions suggests some invisible transmission dynamic. Hence, broad-minded and vigilant epidemiological attention to the current MPX epidemic is mandatory. Therefore, this review was compiled to highlight the epidemiological dynamic, global host ranges, and associated risk factors of MPX, concentrating on its epidemic potential and global public health threat.