Epigenetics refers to how life is regulated beyond the gene sequence through modifications of DNA-associated histone proteins, DNA, and small non-coding RNAs. The human genome is organized as a nucleoprotein filament composed of DNA, histone proteins, non-histone proteins, and non-coding RNAs. During cell division, DNA is condensed into chromosomes, while in interphase, functional chromatin exists as individual territories. Chromatin folding and unfolding regulate genome function through epigenetic modifications, which are reversible and influenced by the cell's metabolic state. Enzymes such as DNA methyltransferases (DNMT), lysine acetyltransferases (KAT), and lysine methyltransferases (KMT) are responsible for DNA and histone modifications. These enzymes, known as "Writers," are essential for epigenetic regulation. "Erasers" remove modifications to maintain reversibility, while "Readers" recognize modifications and recruit factors. These mechanisms are crucial for cellular homeostasis, which is dysregulated in cancer. Cancer is a metabolic disorder driven by gene mutations and dysregulated epigenetic machinery. Epigenetic modifications are important targets for new cancer therapies. Historically, chemotherapeutics targeting the epigenome have been used. Nucleotide analogues are commonly used, targeting DNA methyltransferases. Histone deacetylases (HDACs), acetyltransferases, and lysine methyltransferases are also overexpressed in cancer cells. Chromatin remodeling machineries are often mutated in cancer. Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer, which can be reversed by EZH2 inhibitors. Epigenetic machineries are promising targets for treating triple-negative breast cancer. Inhibitors of DNA methyltransferases, histone methyltransferases, and histone deacetylases are promising for cancer therapy. Many of these inhibitors are already approved or in clinical trials. Natural compounds are being screened for epigenetic modulation. Epigenetic modulators like garcinol can enhance cancer cell apoptosis when used with chemotherapeutics. Epigenetic modifications may also serve as diagnostic markers for cancer progression and prognosis.Epigenetics refers to how life is regulated beyond the gene sequence through modifications of DNA-associated histone proteins, DNA, and small non-coding RNAs. The human genome is organized as a nucleoprotein filament composed of DNA, histone proteins, non-histone proteins, and non-coding RNAs. During cell division, DNA is condensed into chromosomes, while in interphase, functional chromatin exists as individual territories. Chromatin folding and unfolding regulate genome function through epigenetic modifications, which are reversible and influenced by the cell's metabolic state. Enzymes such as DNA methyltransferases (DNMT), lysine acetyltransferases (KAT), and lysine methyltransferases (KMT) are responsible for DNA and histone modifications. These enzymes, known as "Writers," are essential for epigenetic regulation. "Erasers" remove modifications to maintain reversibility, while "Readers" recognize modifications and recruit factors. These mechanisms are crucial for cellular homeostasis, which is dysregulated in cancer. Cancer is a metabolic disorder driven by gene mutations and dysregulated epigenetic machinery. Epigenetic modifications are important targets for new cancer therapies. Historically, chemotherapeutics targeting the epigenome have been used. Nucleotide analogues are commonly used, targeting DNA methyltransferases. Histone deacetylases (HDACs), acetyltransferases, and lysine methyltransferases are also overexpressed in cancer cells. Chromatin remodeling machineries are often mutated in cancer. Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer, which can be reversed by EZH2 inhibitors. Epigenetic machineries are promising targets for treating triple-negative breast cancer. Inhibitors of DNA methyltransferases, histone methyltransferases, and histone deacetylases are promising for cancer therapy. Many of these inhibitors are already approved or in clinical trials. Natural compounds are being screened for epigenetic modulation. Epigenetic modulators like garcinol can enhance cancer cell apoptosis when used with chemotherapeutics. Epigenetic modifications may also serve as diagnostic markers for cancer progression and prognosis.