Glutamine addiction in tumor cells is a critical aspect of cancer metabolism, as tumor cells rely heavily on glutamine for biosynthesis of amino acids, fatty acids, nucleotides, and other essential molecules. This dependency is closely linked to the survival and progression of cancer cells, making glutamine metabolism a promising target for cancer treatment. Tumor cells undergo metabolic reprogramming due to genetic mutations and altered signaling, which allows them to adapt to nutrient-deprived environments. This reprogramming increases glutamine uptake and metabolism, enabling the production of energy and biosynthetic intermediates necessary for uncontrolled proliferation. Oncogenes such as C-MYC, KRAS, HIF, and p53 play significant roles in regulating glutamine metabolism. C-MYC enhances glutamine uptake and metabolism, promoting tumor growth and survival. KRAS increases glutamine anabolism, supporting tumor cell proliferation. HIF-1α and HIF-2α regulate glutamine metabolism under hypoxic conditions, influencing tumor cell survival and progression. p53, on the other hand, can enhance mitochondrial respiration and glutamine metabolism to protect tumor cells from oxidative stress. Glutamine metabolism is regulated by key enzymes such as glutaminase (GLS), which converts glutamine to glutamate. GLS1 is overexpressed in many cancers and is a target for therapeutic intervention. Inhibiting GLS1 has shown promise in reducing tumor growth. Additionally, glutamine is involved in the synthesis of glutathione, a powerful antioxidant that protects tumor cells from oxidative damage. The mTORC1 pathway is also closely linked to glutamine metabolism. mTORC1 regulates cell proliferation, growth, and metabolism by sensing amino acids, growth factors, and oxygen. Glutamine can activate mTORC1, leading to increased cell growth and proliferation. Inhibiting mTORC1 or its upstream regulators can be a potential therapeutic strategy. Various glutamine inhibitors, such as CB-839 and BPTES, are being developed to target glutamine metabolism in cancer cells. These inhibitors show promise in preclinical studies but face challenges related to solubility, toxicity, and clinical application. Future research aims to improve the efficacy and safety of these inhibitors through prodrug development, nanocapsules, and targeted drug delivery systems. Targeting glutamine metabolism represents a promising approach for cancer treatment, with ongoing research exploring its potential in combination therapies.Glutamine addiction in tumor cells is a critical aspect of cancer metabolism, as tumor cells rely heavily on glutamine for biosynthesis of amino acids, fatty acids, nucleotides, and other essential molecules. This dependency is closely linked to the survival and progression of cancer cells, making glutamine metabolism a promising target for cancer treatment. Tumor cells undergo metabolic reprogramming due to genetic mutations and altered signaling, which allows them to adapt to nutrient-deprived environments. This reprogramming increases glutamine uptake and metabolism, enabling the production of energy and biosynthetic intermediates necessary for uncontrolled proliferation. Oncogenes such as C-MYC, KRAS, HIF, and p53 play significant roles in regulating glutamine metabolism. C-MYC enhances glutamine uptake and metabolism, promoting tumor growth and survival. KRAS increases glutamine anabolism, supporting tumor cell proliferation. HIF-1α and HIF-2α regulate glutamine metabolism under hypoxic conditions, influencing tumor cell survival and progression. p53, on the other hand, can enhance mitochondrial respiration and glutamine metabolism to protect tumor cells from oxidative stress. Glutamine metabolism is regulated by key enzymes such as glutaminase (GLS), which converts glutamine to glutamate. GLS1 is overexpressed in many cancers and is a target for therapeutic intervention. Inhibiting GLS1 has shown promise in reducing tumor growth. Additionally, glutamine is involved in the synthesis of glutathione, a powerful antioxidant that protects tumor cells from oxidative damage. The mTORC1 pathway is also closely linked to glutamine metabolism. mTORC1 regulates cell proliferation, growth, and metabolism by sensing amino acids, growth factors, and oxygen. Glutamine can activate mTORC1, leading to increased cell growth and proliferation. Inhibiting mTORC1 or its upstream regulators can be a potential therapeutic strategy. Various glutamine inhibitors, such as CB-839 and BPTES, are being developed to target glutamine metabolism in cancer cells. These inhibitors show promise in preclinical studies but face challenges related to solubility, toxicity, and clinical application. Future research aims to improve the efficacy and safety of these inhibitors through prodrug development, nanocapsules, and targeted drug delivery systems. Targeting glutamine metabolism represents a promising approach for cancer treatment, with ongoing research exploring its potential in combination therapies.