Stroke is an often underrecognized albeit significant complication in patients with brain cancer, arising from the intricate interplay between cancer biology and cerebrovascular health. This review delves into the multifactorial pathophysiological framework linking brain cancer to elevated stroke risk, with particular emphasis on the crucial role of the neurotoxic microenvironment (NTME). The NTME, characterized by oxidative stress, neuroinflammation, and blood–brain barrier (BBB) disruption, creates a milieu that promotes and sustains vascular and neuronal injury. Key pathogenic factors driving brain cancer-related stroke include cancer-related hypercoagulability, inflammatory and immunological mechanisms, and other tumor-associated processes, including direct tumor compression, infection-related sequelae, and treatment-related complications. Recent advances in genomic and proteomic profiling present promising opportunities for personalized medicine, enabling the identification of biomarkers—such as oncogenes and tumor suppressor genes—that predict stroke susceptibility and inform individualized therapeutic strategies. Targeting the NTME through antioxidants to alleviate oxidative stress, anti-inflammatory agents to mitigate neuroinflammation, and therapies aimed at reinforcing the BBB could pave the way for more effective stroke prevention and management strategies. This integrative approach holds the potential to reduce both the incidence and severity of stroke, ultimately improving clinical outcomes and quality of life for brain cancer patients. Further research and well-designed clinical trials are essential to validate these strategies and integrate them into routine clinical practice, thereby redefining the management of stroke risk in brain cancer patients.