Cancer is increasingly recognized as a disease driven not only by genetic mutations but also by profound epigenetic alterations. DNA methylation, histone modifications, and non-coding RNAs regulate gene expression programs that control tumor initiation, progression, metastasis, and therapy resistance. Although epigenetic drugs such as DNA methyltransferase inhibitors and histone deacetylase inhibitors have entered clinical practice, their therapeutic success remains limited due to non-selective activity, dose-dependent toxicity, and heterogeneous patient response. Recent advances in epigenomic profiling have revealed cancer-specific and subtype-specific epigenetic signatures that may serve as predictive biomarkers for treatment response. This paper proposes a biomarker-guided precision epigenetic therapy framework, integrating epigenetic profiling with targeted therapeutic strategies to improve clinical efficacy and safety. We discuss current knowledge in cancer epigenetics, limitations of existing epigenetic therapies, emerging biomarkers, and rational combination strategies. Finally, we outline future research directions necessary for translating precision epigenetic medicine into
routine oncology practice.