Metal-based nanomaterials achieve tumor treatment strategies by overcoming the blood-brain barrier of glioma and responding to the tumor microenvironment.

Glioblastoma (GBM) continues to be the most lethal form of primary brain tumor. Therapeutic efficacy is significantly hindered by the presence of the blood-brain barrier (BBB) and the complex tumor microenvironment (TME), both of which contribute to the development of drug resistance. Metal-based nanomaterials have demonstrated considerable promise as therapeutic agents capable of overcoming these critical barriers. This article provides a systematic review of recent advances in the development of TME-responsive metal-based nanomaterials for GBM diagnosis and treatment. To accomplish controlled drug release, enhance imaging performance, and enable synergistic therapeutic approaches-including chemodynamic therapy (CDT), piezodynamic therapy (PZDT), gene therapy, and immunotherapy (IMT), and so on-the role of artificial intelligence (AI) in supporting treatment strategies is also examined. The discussion highlights how these nanomaterials are engineered to exploit distinctive features of the TME. Furthermore, targeted functionalization strategies designed to improve penetration across the BBB are analyzed. Finally, a critical evaluation of translational challenges and potential clinical applications is presented, offering insights that could advance a new paradigm in GBM therapy.