Mucormycosis is an angioinvasive lethal fungal infection in pediatric cancer patients. We present 10-year-old female with relapsed B-cell acute lymphoblastic leukemia undergoing chemotherapy was diagnosed with isolated cerebral mucormycosis (ICM). Despite surgical debridement and liposomal amphotericin B, repeat imaging showed concern for disease progression. Chemotherapy was discontinued and the patient was discharged on salvage therapy oral isavuconazole (ISAV). Over two months later, the patient was unexpectedly clinically stable, and imaging showed near resolution. After confirming continuous disease remission, the patient was restarted on modified chemotherapy. Serial MRI’s during continued chemotherapy showed stable MRI findings. This case illustrates a rare presentation of successful salvage monotherapy ISAV for this deadly infection with complete remission for relapsed leukemia.