Background: Lumpy skin disease (LSD) is a highly infectious and economically important transboundary disease that is rapidly spreading to the globe. The disease causes high morbidity and a low mortality rate of infection. The animals show acute or chronic illnesses depending on the immune responses of the hosts. The economic burden of LSD manifested the poor-quality hides, a drop in milk and meat production, abortion, and death. Methods: This systematic literature review was accomplished according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature on lumpy skin disease has been explored over the last two decades and searched keywords on online databases such as Google Scholar, PubMed, and Scopus. Both automated and manual searching tools were used to screen the articles. The literature published other than English was rejected during the screening process. Conference papers were excluded during the screening. Results: LSD is transmitted by blood-sucking arthropods and is most prevalent in summer and rainy seasons. Exotic-bred cattle and calves are highly susceptible. Although the disease has low mortality, the high mortality of the disease prevails in endemic regions in complicated cases. Calves from unvaccinated cows should be vaccinated at any age, on the other hand, the calves from vaccinated cows should be immunized at 3 months of age. Animals should be vaccinated before the risk period. Strict biosecurity, quarantine, and immunoprophylaxis can reduce the prevalence of the disease. Conclusions: Lumpy skin disease (LSD) is an acute infectious and contagious disease affecting cattle and water buffaloes. The disease causes serious economic loss due to decreased production, skin problems, and mortality in complicated cases. Further details on genetic characterization, transmission dynamics, and host-pathogen interaction should be performed to prevent the prevalence of the disease in emerging or re-emerging countries.