Monkeypox is a zoonotic viral disease of public health concern, after almost forty years of no case report, its re-emergence in 2017 at Bayelsa state, Nigeria creates public anxiety, morbidity as well as mortality. It affects susceptible individual of all age groups and gender and consequently, the prevalence is continuously increasing. The causative agent of this disease is Monkeypox virus (MPXV), which belongs to the family Poxviridae and the genus Orthopoxvirus. Its genome is linear double-stranded DNA (≈197kb). This article aimed to make an overview on transmission, clinical manifestation, the factors responsible for the re-emergence and spread of Monkeypox virus in Nigeria. It is transmitted through animals to human (zoonotic transmission) and human to human with broad signs and symptoms after short incubation period including headache, fever, swollen lymph nodes, muscle pain, and tiredness, followed by rashes which develops into blisters and crusts over. Among the predisposing factors of the re-emergence of Monkeypox in Nigeria include but not limited to: Increased bush meat consumption, lack of smallpox vaccination coverage or declined of immunity in vaccinated individual over time and accumulation of young population, climate change and deforestation, inadequate health and research infrastructures. The re-emergence is beyond public health concern for Nigeria but has potential global health threat and implications. It is re-emergence after several years of no case report, further justify the need for the scientific community to extend their research work on this virus, especially for the development of specific preventive measures, therapies, and control strategies.