Background:Following the recent surge in monkeypox cases worldwide, vaccines have gained popularity due to their protective role against the disease in the absence of specific pharmacological therapies for the disease. This article explores the possible challenges associated with the treatment and prevention of monkeypox with special emphasis on cardiovascular concerns relating to vaccines, warranting further investigation and research.Methods:Multiple electronic databases from inception till October 2022 were searched to find articles reporting the cardiovascular adverse events associated with monkeypox immunization.Results:Smallpox vaccines ACAM2000, JYNNEOS, and modified vaccinia Ankara have been used for monkeypox. ACAM2000 has been reported to have major cardiovascular adverse events such as myocarditis, dilated cardiomyopathy, and heart failure. Whereas JYNNEOS and modified vaccinia Ankara are associated with minor cardiovascular adverse events such as tachycardia, palpitation, electrocardiogram changes such as T wave inversion, and ST elevation.Conclusions:Despite having cardiovascular issues with the existing vaccines, clinicians and public health experts should measure the risk benefit aspect of smallpox vaccines to decide whether to go for mass immunization or not. Based on the lessons learned from the COVID-19 pandemic, immunization will be a better strategy to halt the monkeypox spread throughout the globe. However, further research is needed to determine the exact incidence and susceptibility to develop cardiovascular complications among monkeypox immunized individuals.