The human genome harbors >1,600 evolutionarily conserved RNA-binding proteins (RBPs), with extensive multi-omics investigations documenting their pervasive dysregulation in malignancies ranging from glioblastoma to melanoma. These RBPs are integral to the complex regulatory networks governing hallmark cancer processes. Recent studies have investigated the multifaceted contributions of RBPs to tumorigenesis, tumor metabolism, the tumor-immune microenvironment, and resistance to therapy. This complexity is further compounded by the intricate regulation of RNA function at various levels by RBPs, as well as the post-translational modifications of RBPs, which improve their functional capacity. Moreover, numerous RBP-based therapeutics have emerged, each underpinned by distinct molecular mechanisms that extend from genomic analysis to the interference of RBPs' function. This review aims to provide a comprehensive overview of the recent progress in the meticulous roles of RBPs in brain tumors and to explore potential therapeutic interventions targeting these RBPs, complemented by a discussion of innovative techniques emerging in this research field. Advances in deciphering RNA-RBP interactomes and refining targeted therapeutic strategies are revealing the transformative potential of RBP-centric approaches in brain tumor treatment, establishing them as pivotal agents for overcoming current clinical challenges.