Kaposi’s sarcoma-associated herpes virus (KSHV) is the formation of a life-long persistent infection, which causes several clinical, epidemiological, and contagious diseases. KSHV is primarily transmitted through saliva, although vertical, sexual, blood, and transplant-related transmission are also possible. KSHV is responsible for causing Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. KSHV-combined malignancies are mainly present in individuals with primary and acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) and iatrogenic immunosuppression in organ transplant recipients. Prophylactic vaccines characteristically stimulate an individual’s humoral immune system to form neutralizing antibodies against the KHSV surface glycoproteins and mediating the contagious agent’s entry. The role of neutralizing antibodies for inhibiting KSHV (or) KSHV-combined malignancies has not been determined. The vaccine is the most effective method to prevent viral diseases, but to date, there is no approved prophylactic vaccine available against KSHV. There are no preclinical or clinical vaccine experiments stated in the past four decades, despite the AIDS epidemic. KSHV vaccine would play a significantly advantageous role for at-risk patients. Therefore, the present study focuses on the advances in the field of computational biology helping in the design of potential vaccines for KSHV.