Epstein–Barr virus (EBV) is a significant human tumor virus, infecting an estimated 90% of the global population. EBV has evolved various epigenetic mechanisms to affect its host and contribute to the development and progression of several cancers. This review highlights four prominent epigenetic regulatory mechanisms that facilitate host-virus interactions during EBV infection, persistence, and associated diseases. These mechanisms include histone modifications, DNA methylation patterns, microRNA targeting of host cell factors, and chromatin remodeling. The review also explores how epigenetic profiles of the host are altered in EBV-associated cancers, providing insights into the precise ways EBV interacts with its host to cause disease. Understanding these epigenetic mechanisms is crucial for advancing research on EBV and developing therapeutic interventions.Epstein–Barr virus (EBV) is a significant human tumor virus, infecting an estimated 90% of the global population. EBV has evolved various epigenetic mechanisms to affect its host and contribute to the development and progression of several cancers. This review highlights four prominent epigenetic regulatory mechanisms that facilitate host-virus interactions during EBV infection, persistence, and associated diseases. These mechanisms include histone modifications, DNA methylation patterns, microRNA targeting of host cell factors, and chromatin remodeling. The review also explores how epigenetic profiles of the host are altered in EBV-associated cancers, providing insights into the precise ways EBV interacts with its host to cause disease. Understanding these epigenetic mechanisms is crucial for advancing research on EBV and developing therapeutic interventions.