The threat of the emergence of potential pandemics in the future has been looming ever since the world witnessed the worst-ever public health catastrophe following the coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The COVID-19 pandemic affected billions of people killing millions of people throughout the world. Now, we have been noticing an alarming rise in the cases of mpox disease caused by Mpox virus (MPXV). Although discovered in 1958, mpox was largely confined to monkeys before causing the first human infection in 1970. The MPXV is demonstrating a complex transmission behavior as noted by its discovery first in Denmark in monkeys imported from Singapore (Asia) and later spreading to humans causing repeated re-emergence. The virus was confined to the African nations including the Democratic Republic of Congo (DRC) before reemerging in the United States of America in 2003 affecting several people who had a history of contact with animals. Following scattered reports from endemic regions, the virus appears to have remerged after approximately two decades in 2022 involving the United States of America (USA) and European countries. The virus has been spreading across the globe as evidenced by its discovery in 60 countries in 2022 to more than 120 countries in the current year. It is therefore essential to improve the understanding of the MPXV, its epidemiology, pathogenicity and virulence, clinical features, and control and preventive measures and increase preparedness to efficiently tackle any future public health emergency.