Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan and brain (...) shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation with various neuroimaging modalities has not yet been reported.Case Report: A 42-year-old left-handed man had increased intracranial pressure, left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function was performed, combined with magnetic resonance imaging -based tractography reconstruction of 6 neural tracts and resting-state functional MRI connectivity of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery. (shrink)