Background: Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare, delayed complication of cranial irradiation characterized by subacute, potentially reversible neurological deficits and distinctive imaging features. Its diagnosis is particularly challenging in patients with metastatic brain disease, where clinical and radiological findings overlap with tumor progression, radiation necrosis, and seizure-related phenomena. Case Presentation: We report the case of a 43-year-old male with stage IV ALK-positive non-small-cell lung adenocarcinoma with extensive brain metastases who developed acute global aphasia and altered mental status following multiple courses of cranial irradiation, including stereotactic radiosurgery, and whole-brain radiation therapy in addition to subtotal resection of a frontal brain lesion. The patient had prolonged systemic disease control with sequential ALK inhibitors but experienced repeated intracranial progression requiring multimodal local therapies. During an acute neurological deterioration in November 2025, neuroimaging demonstrated extensive post-radiation and metastatic changes, and the differential diagnosis included tumor progression, radiation necrosis, and focal status epilepticus. Given the clinical context and imaging limitations, SMART syndrome was suspected. High-dose intravenous corticosteroids led to partial neurological improvement, supporting the diagnosis of radiation-induced cortical dysfunction. Conclusion: This case highlights the diagnostic complexity of SMART syndrome in patients with advanced metastatic brain disease and cumulative radiation exposure.