Resistance to erythropoiesis-stimulating agents (ESAs) presents a formidable challenge in the management of anemia and iron metabolism disorders in patients undergoing hemodialysis. We herein describe the case of a 70-year-old female with chronic kidney disease (CKD) stage 5 who was on maintenance hemodialysis and exhibited resistance to conventional ESA therapy. Despite the administration of high doses of ESA (recombinant human erythropoietin, r-HuEPO, at 18,000 U/week), her hemoglobin levels persistently remained suboptimal (ranging from 97 to 109 g/L), and she demonstrated elevated ferritin levels (between 2471 and 2722 ng/mL), suggesting impaired iron utilization and erythropoietin resistance. The patient was then switched from r-HuEPO to roxadustat, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). This therapeutic transition effectively elevated her hemoglobin levels (from 103 to 130 g/L) and markedly decreased ferritin levels (from 2040 to 497 ng/mL), thereby ameliorating the iron metabolism disorder. This case highlights the efficacy of roxadustat in addressing ESA-resistant renal anemia by optimizing iron metabolism in hemodialysis patients.