Iron homeostasis is crucial in hematological diseases, with the hepcidin molecule regulating its systemic balance by binding to ferroportin, the sole exporter of iron from cells into the blood. The binding of hepcidin to ferroportin leads to its degradation and a decrease in the release of iron, which affects the absorption and distribution of iron in the body. Dysregulation of the hepcidin-ferroportin axis is associated with various pathological conditions, including anemia and hematological malignancies. New therapeutic approaches include agents such as luspatercept, matriptase-2 inhibitors, and anti-hemojuvelin antibodies that modulate erythropoiesis and iron metabolism. The research also highlights the importance of ferroptosis, an iron-dependent cell death, as a potential therapeutic target. The integration of pharmacogenomics and precision medicine can improve the treatment of these diseases. Clinical trials show the promise of these therapies, but also point to the need for further research and development of combination strategies based on biomarker stratification of patients.