Type 2 Diabetes Mellitus (T2DM) and leukemia are two major global health concerns, both contributing significantly to morbidity and mortality. Epidemiological evidence demonstrates a strong correlation between T2DM and an increased risk of leukemia, particularly driven by insulin resistance, hyperglycemia, and the resultant metabolic dysregulation. Key shared risk factors, including obesity and chronic inflammation, create a conducive environment for leukemogenesis, intensifying cancer cell proliferation and resistance to standard therapies. Insulin resistance, in particular, triggers oncogenic pathways such as PI3K/AKT and MAPK, exacerbating the aggressive phenotype seen in leukemia patients with T2DM. Additionally, clonal hematopoiesis of indeterminate potential (CHIP) is implicated in the higher leukemia risk observed in diabetic populations, especially among the elderly. Molecular mechanisms like the insulin-like growth factor (IGF) system further highlight the intricate link between these diseases, promoting survival and proliferation of leukemia cells. The coexistence of T2DM in leukemia patients is associated with poorer prognostic outcomes, including increased susceptibility to infections, reduced survival, and greater treatment resistance. Antidiabetic agents, notably metformin and pioglitazone, show promise in enhancing chemotherapy efficacy and improving patient outcomes by targeting metabolic pathways. These results highlight the need for comprehensive treatment approaches that target both metabolic abnormalities and cancer-related mechanisms in patients suffering from both T2DM and leukemia.