<p>Serine plays a vital role in various metabolic processes including the synthesis of proteins and other amino acids, which are essential for the cell proliferation and growth. Cancer cells either absorb exogenous serine or produce it through the serine synthesis pathway, enabling the generation of intracellular glycine and one-carbon units, which are crucial for nucleotide biosynthesis. This metabolic process, referred to as serine-glycine-one-carbon (SGOC) metabolism, is essential for tumorigenesis and exhibits considerable complexity and clinical significance. Enzymes involved in the SGOC pathway are linked to tumor growth, metastasis, and resistance to therapies. The SGOC pathway is a vital metabolic network that facilitates cell survival and proliferation, especially in aggressive cancers. Understanding how this network is regulated is crucial for tackling tumor heterogeneity and recurrence. This review emphasizes recent advancements in understanding the roles and effects of the SGOC metabolic pathway in the context of cancer progression. Additionally, it outlines the complex influences of the SGOC metabolic pathway on the tumor microenvironment (TME), offering potential strategies to enhance cancer immunotherapy.</p>