This study presents a pioneering exploration into the role of aggrephagy-related genes (ARGs) in glioblastoma (GB), a kind of malignant tumor which is highly invasive and resistant to a series of therapy. Utilizing single-cell sequencing to dissect their influence on the tumor microenvironment (TME) and tumorigenesis. By applying non-negative matrix factorization for dimensionality reduction and clustering of single-cell data, distinct cellular subtypes within the TME influenced by ARGs were identified, uncovering their functions and interactions. The investigation extends to validating the prognostic significance of ARGs and their potential in predicting immunotherapy outcomes. Molecular docking analysis of key ARGs further highlights TUBA1C and UBB as promising therapeutic targets, offering novel insights into GB's complex biology and suggesting a targeted approach for therapy, which is characterized by some crucial pathways in our analysis, including PI3k-akt and TGF-beta pathways. This comprehensive single-cell level examination not only advances our understanding of aggrephagy's role in GB but also proposes new avenues for prognosis and treatment strategies, emphasizing the critical impact of ARGs on the TME and GB progression.