Simple Summary: Since ferroptosis was proposed in 2012, it has been a popular field of study for researchers. So far, the regulatory mechanism of ferroptosis involves many aspects, such as DNA, RNA, and proteins. Accumulating studies have shown that ferroptosis and epigenetic modifications are crucial in multiple diseases. This review provides information on resistance systems to ferroptosis and advanced studies of epigenetic modifications in DNA methylation, RNA methylation, non-coding RNAs, and histone modifications through regulating ferroptosis in cancer and other diseases. A summary of the targets of epigenetic modifications regulating ferroptosis could help identify new prognostic indicators in human diseases and provide potential therapeutic strategies for these diseases. Ferroptosis is a non-apoptotic mode of cell death driven by membrane lipid peroxidation and is characterized by elevated intracellular levels of Fe2+, ROS, and lipid peroxidation. Studies have shown that ferroptosis is related to the development of multiple diseases, such as cancer, neurodegenerative diseases, and acute myeloid leukemia. Ferroptosis plays a dual role in the occurrence and development of these diseases. Ferroptosis mainly involves iron metabolism, ROS, and lipid metabolism. Various mechanisms, including epigenetic regulation, have been reported to be deeply involved in ferroptosis. Abnormal epigenetic modifications have been reported to promote tumor onset or other diseases and resistance to chemotherapy drugs. In recent years, diversified studies have shown that epigenetic modification is involved in ferroptosis. In this review, we reviewed the current resistance system of ferroptosis and the research progress of epigenetic modification, such as DNA methylation, RNA methylation, non-coding RNAs, and histone modification in cancer and other diseases by regulating ferroptosis. [ABSTRACT FROM AUTHOR]