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A woman in her 60s presented with an 8-month history of right-sided facial pain, with new reduced visual acuity, bilateral diplopia, restricted right extraocular movements and red desaturation. Her comorbidities included relapsing–remitting multiple sclerosis, breast cancer and type 2 diabetes mellitus. Imaging showed an aggressive sinonasal process with erosion into the right orbit, skull base and cavernous sinus. Biopsy confirmed invasive fungal sinusitis with septate hyphae and culture identified Aspergillus fumigatus.Initial treatment with amphotericin B was complicated by acute kidney injury, prompting a switch to posaconazole. Due to disease progression, therapy was escalated to isavuconazole, alongside right orbital exenteration and skull-base debridement.At 12 months, she was symptom-free and remains on lifelong isavuconazole; MRI at 16 months showed no recurrence.This case highlights diagnostic challenges, targeted antifungal therapy and multidisciplinary surgical management in advanced sino-orbital aspergillosis, alongside the ethical complexity of choosing radical surgery over palliation with intracranial extension.