Serine and glycine are essential metabolites in cancer biology, providing precursors for proteins, nucleic acids, and lipids crucial for cancer cell growth. Their biosynthesis also influences cellular antioxidant capacity and tumour homeostasis. The glycine cleavage system refuels one-carbon metabolism, a complex network involving folate compounds. Genetic and functional evidence indicates that hyperactivation of the serine/glycine biosynthetic pathway drives oncogenesis. Recent advances in understanding these pathways offer new translational opportunities for drug development, dietary intervention, and biomarker identification. Serine is a central hub in cancer metabolism, supporting anabolic pathways and redox status. De novo serine biosynthesis is a key component of glycolysis-diverting pathways, with phosphoglycerate dehydrogenase (PHGDH) playing a crucial role. PHGDH upregulation is associated with cancer growth and oncogenic transformation. Serine biosynthesis also contributes to the pentose phosphate pathway and TCA cycle, providing intermediates for nucleotide and lipid synthesis. The p53 family, including p53 and p73, regulates serine biosynthesis and metabolic reprogramming in response to stress. p53 helps cancer cells overcome serine starvation, maintaining antioxidant capacity. p73 promotes serine biosynthesis under metabolic stress, supporting cancer cell survival. Both p53 and p73 influence glycolysis-related pathways, enabling cells to respond to metabolic stress. Serine also regulates pyruvate kinase M2 (PKM2), which controls glycolytic rate through allosteric regulation. Serine activates PKM2, enhancing aerobic glycolysis and lactate production, critical for cancer cell growth. Serine fuels glycine biosynthesis, which is essential for one-carbon metabolism, nucleotide biosynthesis, and DNA methylation. One-carbon metabolism cycles carbon units from amino acids, generating essential metabolites for cellular growth. Folate and methionine cycles are central to this process, with SHMT enzymes playing a key role in methyl group transfer. Glycine metabolism is crucial for cancer cell proliferation, with glycine uptake and catabolism promoting tumourigenesis. Targeting glycine metabolism may offer new therapeutic strategies. Antimetabolites, such as methotrexate and pemetrexed, target folate-dependent pathways, inhibiting thymidylate and purine biosynthesis. These drugs are effective against rapidly proliferating tumours. Other approaches aim to modulate epigenetic status or dietary interventions to enhance cancer therapy. Understanding serine and glycine metabolism is crucial for developing targeted therapies. The integration of these pathways into the mutational landscape of cancer cells remains an area of active research. Mathematical models and integrative approaches are needed to explore the therapeutic potential of these metabolic routes. The role of serine and glycine in cancer metabolism highlights the importance of metabolic reprogramming in cancerSerine and glycine are essential metabolites in cancer biology, providing precursors for proteins, nucleic acids, and lipids crucial for cancer cell growth. Their biosynthesis also influences cellular antioxidant capacity and tumour homeostasis. The glycine cleavage system refuels one-carbon metabolism, a complex network involving folate compounds. Genetic and functional evidence indicates that hyperactivation of the serine/glycine biosynthetic pathway drives oncogenesis. Recent advances in understanding these pathways offer new translational opportunities for drug development, dietary intervention, and biomarker identification. Serine is a central hub in cancer metabolism, supporting anabolic pathways and redox status. De novo serine biosynthesis is a key component of glycolysis-diverting pathways, with phosphoglycerate dehydrogenase (PHGDH) playing a crucial role. PHGDH upregulation is associated with cancer growth and oncogenic transformation. Serine biosynthesis also contributes to the pentose phosphate pathway and TCA cycle, providing intermediates for nucleotide and lipid synthesis. The p53 family, including p53 and p73, regulates serine biosynthesis and metabolic reprogramming in response to stress. p53 helps cancer cells overcome serine starvation, maintaining antioxidant capacity. p73 promotes serine biosynthesis under metabolic stress, supporting cancer cell survival. Both p53 and p73 influence glycolysis-related pathways, enabling cells to respond to metabolic stress. Serine also regulates pyruvate kinase M2 (PKM2), which controls glycolytic rate through allosteric regulation. Serine activates PKM2, enhancing aerobic glycolysis and lactate production, critical for cancer cell growth. Serine fuels glycine biosynthesis, which is essential for one-carbon metabolism, nucleotide biosynthesis, and DNA methylation. One-carbon metabolism cycles carbon units from amino acids, generating essential metabolites for cellular growth. Folate and methionine cycles are central to this process, with SHMT enzymes playing a key role in methyl group transfer. Glycine metabolism is crucial for cancer cell proliferation, with glycine uptake and catabolism promoting tumourigenesis. Targeting glycine metabolism may offer new therapeutic strategies. Antimetabolites, such as methotrexate and pemetrexed, target folate-dependent pathways, inhibiting thymidylate and purine biosynthesis. These drugs are effective against rapidly proliferating tumours. Other approaches aim to modulate epigenetic status or dietary interventions to enhance cancer therapy. Understanding serine and glycine metabolism is crucial for developing targeted therapies. The integration of these pathways into the mutational landscape of cancer cells remains an area of active research. Mathematical models and integrative approaches are needed to explore the therapeutic potential of these metabolic routes. The role of serine and glycine in cancer metabolism highlights the importance of metabolic reprogramming in cancer