BACKGROUND : Maximal safe resection is the goal of modern surgical treatment of high-grade gliomas (HGGs) located close to the motor cortex (M1) and/or the corticospinal tract (CST). Preoperative planning based on navigated transcranial magnetic stimulation (nTMS) and fluorescence-guided resection (FGR) using sodium-fluorescein have been separately described to increase the extent of resection (EOR) while preserving the motor pathway. We assessed the efficacy of the combination of these techniques for surgery of motor-eloquent HGGs. METHODS : We enrolled patients with motor-eloquent HGGs operated at the Departments of Neurosurgery of the University of Messina, Italy, and of the Charitè Universitatsmedizin Berlin, Germany, between 2016 and 2019. All patients underwent nTMS mapping of M1, and nTMS-based DTI tractography of CST. Tumor resection was guided by intraoperative neurophysiological mapping (IONM) supported by sodium-fluorescein fluorescence and by intraoperative visualization of the nTMS-based information through neuronavigation. EOR and new permanent motor deficits were compared with a historical control group of patients operated exclusively with IONM guidance. RESULTS : Seventy-nine patients were enrolled, while 55 patients were included as controls. The gross total resection (GTR) rate was significantly higher in patients operated using nTMS + FGR compared with controls (64.5% vs. 47.2%, P=0.04). As well, postoperative new permanent motor deficits were reduced in the study group vs. controls (11.4% vs. 20%). CONCLUSIONS : In this series, the combination of sodium-fluorescein FGR with nTMS-based planning improved surgical treatment of motor-eloquent HGGs. It represents a valuable support to IONM-guided resection, increasing the GTR rate while reducing the occurrence of permanent motor deficits.