Abstract We present a patient diagnosed with nephrotic syndrome and disseminated Nocardia sepsis who was successfully treated with a combination of antibiotics and supportive care, including extracorporeal membrane oxygenation (ECMO). In addition, we performed a literature review of similar cases to provide valuable guidance for future management of cases. The present case demonstrates that ECMO should be included in the comprehensive treatment strategy for disseminated Nocardia sepsis in a patient with nephrotic syndrome. In the present case, Nocardia infection occurred during prolonged steroid and immunosuppressive therapy for nephrotic syndrome, accompanied by septic shock, respiratory failure, multiple organ dysfunction, ventilator-associated pneumonia, catheter-associated bloodstream infection with multidrug-resistant bacteria potentially due to ECMO, and hemopneumothorax. The patient received invasive ventilation, ECMO, hemoperfusion for cytokine removal, and thoracoscopic drainage, which effectively eliminated symptoms to achieve complete recovery. ECMO was applied as a life-support intervention to manage severe respiratory failure and septic shock secondary to disseminated Nocardia sepsis. This approach provides adequate infection control and stabilization of organ functions. The findings suggested that a combination of 2 to 3 antibiotics, including trimethoprim-sulfamethoxazole, imipenem, and linezolid, alleviated the severe Nocardia infections. Therefore, ECMO may serve as a supportive intervention in severe infections but requires careful risk–benefit analysis. In such cases, strict monitoring is required to prevent the occurrence of bloodstream infections, particularly multidrug-resistant bacteria, during ECMO cannulas or circuits.