One-carbon metabolism, involving the folate and methionine cycle, integrates carbon units from amino acids like serine and glycine to generate diverse outputs such as lipid, nucleotide, and protein biosynthesis, redox status maintenance, and methylation substrates. This pathway, once considered a 'housekeeping' process, is now recognized as a potential driver of oncogenesis and linked to cellular epigenetic status. Clinically available agents targeting one-carbon metabolism offer opportunities for precision cancer medicine. The pathway integrates nutrient status, with inputs like glucose and amino acids processed through chemical reactions to support cell growth, proliferation, and maintenance of redox, genetic, and epigenetic status. The folate cycle, methionine cycle, and transsulfuration pathway are key components, with enzymes involved in these pathways playing critical roles in cell growth. Folic acid is reduced to tetrahydrofolate (THF), which participates in carbon atom transfer reactions. The transsulfuration pathway connects to the methionine cycle via homocysteine, and serine can be metabolized to generate glutathione, a major redox-regulating system. Carbon units enter one-carbon metabolism through de novo synthesis or import. Serine can be converted to glycine, which enters the folate cycle. Glycine cleavage systems and threonine metabolism also contribute to one-carbon metabolism. Outputs include biosynthesis of macromolecules, redox balance, and methylation reactions. Methylation reactions, driven by S-adenosylmethionine (SAM), are crucial for histone, DNA, and RNA methylation, as well as protein lysine and arginine methylation. Cancer therapies targeting one-carbon metabolism include folate antagonists like methotrexate and pemetrexed, which inhibit di- and tetrahydrofolate reductase. These drugs disrupt one-carbon metabolism, affecting nucleotide synthesis and methylation. Other chemotherapies, such as 5-fluorouracil (5-FU) and gemcitabine, target nucleotide metabolism. Recent findings suggest that disruptions in one-carbon metabolism may not be effective in all cancers, highlighting the need for further research. One-carbon metabolism is also linked to epigenetic alterations, with SAM-mediated methylation affecting gene regulation. Drugs targeting methyltransferases and demethylases are being evaluated for their potential in cancer therapy. Metabolic enzymes are considered druggable, and targeting key nodes in the one-carbon metabolism pathway is a promising approach for cancer treatment. Metformin, a drug used for diabetes, has shown anti-cancer effects by targeting one-carbon metabolism. Dietary interventions, such as reducing carbohydrate and serine/glycine intake, may also influence cancer progression. Biomarkers related to one-carbon metabolism, such as homocysteine levels, are being explored for cancer diagnosis and treatmentOne-carbon metabolism, involving the folate and methionine cycle, integrates carbon units from amino acids like serine and glycine to generate diverse outputs such as lipid, nucleotide, and protein biosynthesis, redox status maintenance, and methylation substrates. This pathway, once considered a 'housekeeping' process, is now recognized as a potential driver of oncogenesis and linked to cellular epigenetic status. Clinically available agents targeting one-carbon metabolism offer opportunities for precision cancer medicine. The pathway integrates nutrient status, with inputs like glucose and amino acids processed through chemical reactions to support cell growth, proliferation, and maintenance of redox, genetic, and epigenetic status. The folate cycle, methionine cycle, and transsulfuration pathway are key components, with enzymes involved in these pathways playing critical roles in cell growth. Folic acid is reduced to tetrahydrofolate (THF), which participates in carbon atom transfer reactions. The transsulfuration pathway connects to the methionine cycle via homocysteine, and serine can be metabolized to generate glutathione, a major redox-regulating system. Carbon units enter one-carbon metabolism through de novo synthesis or import. Serine can be converted to glycine, which enters the folate cycle. Glycine cleavage systems and threonine metabolism also contribute to one-carbon metabolism. Outputs include biosynthesis of macromolecules, redox balance, and methylation reactions. Methylation reactions, driven by S-adenosylmethionine (SAM), are crucial for histone, DNA, and RNA methylation, as well as protein lysine and arginine methylation. Cancer therapies targeting one-carbon metabolism include folate antagonists like methotrexate and pemetrexed, which inhibit di- and tetrahydrofolate reductase. These drugs disrupt one-carbon metabolism, affecting nucleotide synthesis and methylation. Other chemotherapies, such as 5-fluorouracil (5-FU) and gemcitabine, target nucleotide metabolism. Recent findings suggest that disruptions in one-carbon metabolism may not be effective in all cancers, highlighting the need for further research. One-carbon metabolism is also linked to epigenetic alterations, with SAM-mediated methylation affecting gene regulation. Drugs targeting methyltransferases and demethylases are being evaluated for their potential in cancer therapy. Metabolic enzymes are considered druggable, and targeting key nodes in the one-carbon metabolism pathway is a promising approach for cancer treatment. Metformin, a drug used for diabetes, has shown anti-cancer effects by targeting one-carbon metabolism. Dietary interventions, such as reducing carbohydrate and serine/glycine intake, may also influence cancer progression. Biomarkers related to one-carbon metabolism, such as homocysteine levels, are being explored for cancer diagnosis and treatment