BACKGROUND AND OBJECTIVE:Rhino-orbito-cerebral mucormycosis (ROCM) is a life-threatening fungal infection in immunocompromised or diabetic patients, with mortality between 56 and 73% when the brain is involved. Standard management often fails to halt progression. The MICA (French to summarize the therapeutic strategy combining Mucormycosis management with Invasiveness and Cranial involvement treated with surgery and high-dose Amphotericin B therapy), protocol evaluated whether systematic surgical reassessment combined with liposomal amphotericin B could improve outcomes. METHODS:Patients underwent extensive surgery reaching the skull base, followed by liposomal amphotericin B. Three-month survival was the primary endpoint. Baseline CT/MRI guided staging and resection; second-look imaging and surgery were performed on day 7. RESULTS:Six patients with advanced ROCM (hematologic malignancy or diabetes) were treated. Mortality was 66.7%, driven by rapid progression, skull base invasion and systemic complications; only one patient achieved complete remission. CONCLUSION:Early surgical reassessment and close monitoring may enhance survival, but mortality remains high in cases with hematologic malignancies, and brain involvement. SIGNIFICANCE:This study highlights the critical need for early, multimodal management, optimized control of comorbidities, and enhanced therapeutic strategies, including timely surgical re-exploration, to reduce the persistently high mortality associated with ROCM.