<p>Tumor metastasis is the primary cause of high mortality rates among cancer patients. Invasive tumor cells disseminate through the bloodstream as circulating tumor cells (CTCs) and subsequently colonize secondary organs. In addition to genetic mutations that govern biological processes, epigenetic alterations also regulate tumor cell gene expression and chromosome stability. Dysregulation of these patterns is pivotal to carcinogenesis, tumor progression, and metastasis. This narrative review initiates with a comprehensive overview of the biology of CTCs and the processes that contribute to epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. Subsequently, the impact of epigenetic modifications in CTCs on these metastatic processes during CTC migration, survival, and dissemination will be examined. In addition, the paper presents the implications of targeting epigenetics in CTCs for cancer patients and introduces CTCs as new biomarkers for early detection, prognosis, and targeted therapies to improve patient outcomes.</p> Graphical Abstract <p></p>