This review systematically summarizes the functional mechanisms of key signaling regulators involved in cancer metabolic reprogramming, including mammalian target of rapamycin complex 1 (mTORC1), myelocytomatosis viral oncogene homolog (c-Myc), hypoxia-inducible factor-1α (HIF-1α), activating transcription factor 4 (ATF4), nuclear factor erythroid 2-related factor 2 (NRF2), and sterol regulatory element-binding protein 1 (SREBP1). The gene discussed is NFE2L2; the disease is cancer.