Glioblastoma (GBM) is the most common and aggressive brain tumor with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GBM and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumor microenvironment (TME) immunity. The aim of this study was to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumor samples were collected from 45 patients with histologically confirmed, IDH wild type, GBM (WHO grade IV) and processed to obtain single cell suspensions. Using multiparametric flow cytometry and uni/multivariate analyses, patients were assessed for the correlation of Trm with overall survival (OS) and progression-free survival (PFS). High and low frequency of Trm expressing PD1 and TIM3 was found to be linked to clinical outcome. In fact, low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). The CD8+CD103+ Trm subgroups also resulted age-linked predictors for survival in GBM.