<p>Brain malignancies, such as glioblastoma, remain one of the most aggressive and difficult-to-treat cancers because of their heterogeneity, invasive growth, and resistance to conventional therapy. Significant recent progress in the treatment of these diseases has been associated with the development of gene and cell technologies, which open up new possibilities for targeted therapy, immunotherapy, and personalized approaches. The review systematically summarizes the data on current treatment strategies, including gene therapy, cell therapy, and combined approaches. Particular attention is paid to preclinical and clinical studies, as well as the prospects for overcoming major limitations, such as the blood–brain barrier, the immunosuppressive tumor microenvironment, and toxicity. Analysis of the literature demonstrates that integration of gene and cell technologies could provide a basis for developing effective treatments aimed at improving the survival of patients with central nervous system tumors.</p>