Abstract: Human cytomegalovirus (HCMV) infection poses significant morbidity and/or mortality risks for individuals with compromised immune systems, rendering it one of the most prevalent congenital infections worldwide. The pursuit of HCMV vaccines has spanned over five decades, with clinical trials primarily focusing on various vaccine candidates, including live attenuated vaccines, viral vectored vaccines, subunit vaccines, peptide vaccines, DNA vaccines, RNA vaccines, and viral-like particle vaccines, usually accompanied by the use of adjuvants. Although the development of vaccines against HCMV is being actively promoted, there are still numerous obstacles and challenges persisting in the research process, due to unique pathogenic characteristics and infection mechanisms of HCMV. Based on the summarized research progress, this article analyzes and discusses the faced challenges and potential approaches to provide valuable insights and guidance for the exploration and development of new vaccines candidates, and ultimately achieve prevention and control of HCMV infection.