Zygomycosis can manifest as severe infections, particularly in immunocompromised patients, which can be nosocomial in nature resulting from complications of invasive procedures. We report the case of a 65-year-old woman with a medical history of unclassified inflammatory rheumatism who underwent arteriovenous extracorporeal membrane oxygenation because of a myocardial failure following the drainage of a tuberculous tamponade. This procedure was complicated by a superinfection of the scarpa which revealed a disseminated zygomycosis with renal involvement. A favorable outcome was achieved after 15 months of antifungal therapy involving the use of liposomal amphotericin B followed with posaconazole which involved the close monitoring of the concentrations of this antifungal. Extracorporeal membrane oxygenation is a frequent procedure which could be complicated with severe fungal nosocomial infections such as zygomycosis. The outcome of such complication can be favorable with the utilization of new antifungal therapies.