Wernicke’s encephalopathy (WE), a neurological emergency caused by thiamine deficiency, represents a rare but life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study details the nurse-led management of a 50-year-old man with acute myelomonocytic leukemia with eosinophilia (AML-M4Eo) who developed WE post-transplant. A structured nursing protocol was implemented, comprising comprehensive neurological monitoring (including consciousness and cranial nerve assessments), high-dose intravenous thiamine supplementation, individualized combined enteral and parenteral nutrition with gradual transition to oral intake, infection and bleeding prophylaxis, and psychological support using validated screening tools. After 27 days of integrated care, the patient achieved complete neurological recovery (Glasgow Coma Scale improved from 10 to 15), normalized thiamine levels (22.9 ng/mL), significant nutritional improvement, and fusion gene clearance. At the three-month follow-up, he maintained relapse-free status with substantially enhanced quality of life. This case emphasizes the vital role of systematic, nurse-driven interventions, incorporating early detection, targeted nutrient repletion, stepped nutritional rehabilitation, and psychosocial support, in optimizing WE outcomes post-allo-HSCT, supporting the integration of such multidimensional care into standard transplant protocols.