Tumorigenesis is driven by the accumulation of genetic and epigenetic modifications which alter the 3D structure of the genome, changing its function and gene expression. Epigenetic alterations are mostly stable and heritable modifications in gene expression caused by chemical changes of DNA or related regulatory/structural proteins without altering the primary DNA sequence. The patterns of these modifications are epigenome or epigenetic landscape. Complex interactions between epigenetics and genetics play a critical role in the development and progression of most cancers through loss of control of cell proliferation, cancer heterogeneity, and metastasis. A better understanding of these epigenetic processes underlying tumorigenesis will help us to refine diagnosis, prognosis, and future genetic and epigenetic target therapies for cancer treatment. Several epigenetic agents (epidrugs) are currently available for the standard treatment of various cancers, and many other inhibitors are under development for the treatment and management of cancers resistant to conventional therapies.