BACKGROUND: Chimeric antigen receptor T (CAR-T) therapy for glioblastoma involves critically evaluating progress, effectiveness, and challenges. By examining current research, clinical trials, and emerging trends, the analysis highlights clinical outcomes and biological insights that demonstrate the therapeutic potential of CAR-T cells, along with technological innovations aimed at enhancing their efficacy and safety. However, significant obstacles such as overcoming the blood-brain barrier and managing severe side effects like cytokine release syndrome remain. METHODS: A systematic search using PubMed, Scopus, Web of Science, and Google Scholar from 2010 to 2024 has been conducted. Search terms included "CAR-T," "glioblastoma," "immunotherapy," and "clinical trials." Inclusion criteria were English-language studies focusing on CAR-T applications in glioblastoma. Exclusion criteria included non-peer-reviewed articles and preclinical-only studies. FINDINGS: The findings suggest promising prospects for integrating CAR-T cell therapy into existing glioblastoma treatment paradigms, emphasizing the need for continued research and innovation in genetic engineering and combination therapies to fully realize the potential of CAR-T cells in transforming glioblastoma treatment. CONCLUSIONS: CAR-T cell therapy offers groundbreaking potential in transforming glioblastoma treatment by harnessing the immune system to target and destroy cancer cells.