Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy.

The relationship between the gut microbiota and the central nervous system has gained attention as a biological axis that may influence the development of several neurological disorders. Recent evidence integrating genomic, neurobiological, and microbiota research shows how bacterial composition, host genetic variability, and the mechanisms of the microbiota-gut-brain axis interact in conditions such as autism spectrum disorder, epilepsy, and schizophrenia. These interactions function through neural, metabolic, and immunological related pathways involving intestinal and blood-brain barrier permeability. Genome-wide association studies (GWAS) and Mendelian randomization analyses highlight shared immunogenetic pathways that may shape both microbial profiles and neurological susceptibility. Consistent patterns of dysbiosis and alterations in neuroactive metabolites have also been reported, linking microbiota changes to neuroinflammation and disrupted neuronal signaling. This review synthesizes the current evidence supporting the integration of the microbiota-gut-brain axis and its underlying communication pathways. It also outlines the present therapeutic strategies for neurological disorders such as autism spectrum disorder, epilepsy, and schizophrenia, highlighting their potential to modulate neurological function. Additionally, it discusses the existing limitations in the field and offers insights into future research directions within this rapidly evolving area.