<p>Glioblastoma (GB) is among the most aggressive and treatment-resistant brain tumors, largely due to its heterogeneous tumor microenvironment (TME) and the protective nature of the blood–brain barrier (BBB). Recent advances have highlighted the therapeutic potential of neural stem cells (NSCs), which possess tumor-homing capabilities that enable them to selectively migrate toward and infiltrate GB sites. Engineered NSCs can deliver therapeutic agents, including oncolytic viruses, prodrug-converting enzymes, and genetic materials, offering targeted treatment while minimizing systemic toxicity. Preclinical studies have demonstrated NSCs' promise in enhancing drug delivery, modulating the TME, and promoting anti-tumor immune responses. However, translational hurdles persist, including tumor heterogeneity, species-specific immune responses, and challenges in ensuring long-term safety. Emerging strategies—such as genetic modification to improve tumor targeting and the incorporation of biomaterials to enhance retention—are under investigation. Integrating personalized medicine approaches may further optimize NSC-based therapies by tailoring treatment to individual patient profiles. While significant barriers remain, ongoing research may ultimately establish NSCs as a viable and effective platform for GB therapy.</p> Graphical Abstract <p><i>Engineered NSC for GB</i> GB, an aggressive brain tumor, is being tackled with neural stem cells (NSCs) that are engineered to infiltrate tumor sites, showing potential to enhance drug delivery and modulate the tumor microenvironment for future personalized treatments. Despite the challenges, ongoing translational research actively addresses tumor heterogeneity. </p>