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Immunotherapy is rapidly emerging as a promising approach against cancer. In the last decade, various immunological mechanisms have been targeted to induce an increase in the immune response against cancer cells. However, despite promising results, many patients show partial response, resistance, or serious toxicities. A promising way to overcome this is the use of immunotherapeutic approaches, in combination with other potential therapeutic approaches. Aberrant epigenetic modifications play an important role in carcinogenesis and its progression, as well as in the functioning of immune cells. Thus, therapeutic approaches targeting aberrant epigenetic mechanisms and the immune response might provide an effective antitumor effect. Further, the recent development of potent epigenetic drugs and immunomodulators gives hope to this combinatorial approach. In this review, we summarize the synergy mechanism between epigenetic therapies and immunotherapy for the treatment of cancer, and discuss recent advancements in the translation of this approach.