EZH2/HSP90-IN-29 is a potent dual inhibitor of EZH2 and HSP90, with IC50s of 6.29 nM and 60.1 nM, for EZH2 and HSP90, respectively, that induces M-phase cell cycle arrest, promotes apoptosis/necrosis-related gene expression, and inhibits ROS catabolism. It crosses the blood-brain barrier and can show potential as a tractable anti-GBM agent for glioblastoma research.