Background Intracerebral Cladophialophora bantiana may carry up to a 70% mortality rate despite advances in surgical resection capabilities and the use of both systemic and intrathecal antifungal treatments. Objectives The authors examined a retrospective case series of two patients with intracerebral infection from the rare, neurotropic fungus Cladophialophora bantiana and conducted a literature review to evaluate optimal therapies. Patients/Methods At our institution, the patients' cases presented with raised intracranial features of headache, visual field cut, and/or memory loss, with a correspondingly wide variety of radiological differential diagnoses. It was the microbiological, histopathological, and genomic identification of C. bantiana that ensured targeted, individualized patient therapies. Results and Conclusions Successful treatment depends on obtaining a complete surgical resection, an accurate microbiological diagnoses for mold identification, and an effective long-term, personalized antifungal treatment. Close radiographic surveillance is necessary to ensure complete eradication of pheoid fungi.