The transcription factor Myc is crucial for metabolic reprogramming in activated T lymphocytes. Upon T cell activation, the metabolic pathways shift from fatty acid β-oxidation and pyruvate oxidation via the TCA cycle to aerobic glycolysis, PPP, and glutaminolysis. This metabolic reprogramming is associated with a global change in the metabolic transcriptome, driven by the induction of endogenous Myc and HIF1α. Acute deletion of Myc inhibits activation-induced glycolysis and glutaminolysis, impairs T cell growth and proliferation, and reduces the expression of metabolic genes. Myc-dependent glutaminolysis is coupled with multiple biosynthetic pathways, including nucleotide, amino acid, and polyamine biosynthesis. A novel Myc-dependent metabolic pathway links glutaminolysis to ornithine and polyamine biosynthesis, providing an alternative source of polyamines essential for T cell proliferation. These findings highlight the role of Myc in coordinating metabolic resources and pathways to support T cell growth and proliferation.The transcription factor Myc is crucial for metabolic reprogramming in activated T lymphocytes. Upon T cell activation, the metabolic pathways shift from fatty acid β-oxidation and pyruvate oxidation via the TCA cycle to aerobic glycolysis, PPP, and glutaminolysis. This metabolic reprogramming is associated with a global change in the metabolic transcriptome, driven by the induction of endogenous Myc and HIF1α. Acute deletion of Myc inhibits activation-induced glycolysis and glutaminolysis, impairs T cell growth and proliferation, and reduces the expression of metabolic genes. Myc-dependent glutaminolysis is coupled with multiple biosynthetic pathways, including nucleotide, amino acid, and polyamine biosynthesis. A novel Myc-dependent metabolic pathway links glutaminolysis to ornithine and polyamine biosynthesis, providing an alternative source of polyamines essential for T cell proliferation. These findings highlight the role of Myc in coordinating metabolic resources and pathways to support T cell growth and proliferation.