Brain gliomas represent the most frequent primary malignant tumors of the central nervous system. Current guidelines of treatment at initial diagnosis recommend maximal safe tumor resection while preserving the neurological functions, followed by radio and chemotherapy based on tumor IDH status and grade. Nevertheless, despite the aggressive treatment and the refinements of pre- and intraoperative diagnostic and therapeutic tools, the prognosis remains dismal both for low- and high-grade gliomas. Therefore, the main issue of gliomas surgery is in the rationale behind the strategy of treatment: to prefer the widest extent of resection or the preservation of the neurological functions? A longer life or a better quality of life? The goal is a tailored “onco-functional balance.” For this purpose, a detailed knowledge of the preoperative individual anatomo-functional cerebral organization, intraoperative cortico-subcortical connectivity, along with the neuroplasticity after tumor resection, are mandatory. This brief chapter focuses on the concept of onco-functional or neuro-oncological balance and its applications in the glioma’s treatment.