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Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor patient prognosis. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in GBM pathogenesis, particularly through their interactions with RNA-binding proteins (RBPs). These interactions form complex regulatory networks that influence multiple GBM hallmarks, such as sustained proliferation, induction of angiogenesis, and immune evasion. Additionally, these interactions play a pivotal role in maintaining glioma stem-like cells, a subpopulation responsible for tumor recurrence and resistance to conventional therapies. Understanding the mechanistic basis of lncRNA-RBP interactions offers promising opportunities for therapeutic intervention. Targeting these networks could enable the development of novel and more effective treatment strategies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNA-RBP complexes promote GBM development.