Monkeypox is an emerging zoonotic disease caused by the monkeypox virus (MPXV) and shares similarities with the other Orthopoxviruses. This review aimed to explore the morphology of MPXV, clinical manifestations, and mitigation strategies in the developing nations. Clinically, MPXV resembles smallpox. It has an unidentified natural host, despite it has been isolated from the rope squirrels and Sooty mangabeys. Transmission occurs through the respiratory excretions, saliva, contact with lesions, and potentially via the feces. The disease comprises a prodromal phase and subsequent skin rash. Originating in 1959 following a monkey outbreak in Copenhagen's research institute; the initial human case was documented in 1970 in the Democratic Republic of Congo. The virus subsequently dispersed globally; impacting several nations such as UK, USA, Israel, and Singapore. Thus, in addition to the healthcare infrastructure, combating monkeypox in the developing countries requires bolstering the disease surveillance, public awareness, diagnostic capabilities, and vaccination campaigns. Sustainable international collaboration and extensive scientific investigations are crucial for safeguarding the public health and preventing further spread of this viral disease.