In this article, it is demonstrated that targeting the duodenal Hif2α‐Fpn axis as a novel strategy to improve refractory hepcidin‐activated anemias, including iron‐refractory iron‐deficiency anemia (IRIDA), inflammatory anemia and chemotherapy‐induced anemia, in mice, which provides compelling evidence for further clinical translation. The gene discussed is SLC40A1; the disease is anemia.