<p>Gliomas, particularly glioblastoma (GBM), show limited and inconsistent responses to immunotherapy. This resistance reflects a combination of tumor-intrinsic programs and microenvironmental barriers that restrict antigen presentation, sustain immune checkpoints, and impair effective antitumor immunity. Post-translational modifications (PTMs) have emerged as important regulators of these processes. Phosphorylation, ubiquitination, SUMOylation, and glycosylation regulate the stability, trafficking, maturation, and turnover of immune-related proteins, especially programmed death-ligand 1 (PD-L1), and affect antigen-presentation pathways. Acetylation and methylation reshape immune resistance through chromatin remodeling, transcriptional control, and IDH mutation-associated epigenetic programs. In parallel, metabolism-linked PTMs, including lactylation, palmitoylation, and succinylation, connect hypoxia, glycolysis, lipid signaling, and metabolite accumulation to myeloid suppression, phagocytic escape, ferroptosis resistance, and vascular remodeling. These mechanisms rarely act alone; instead, they form interconnected regulatory layers that help maintain an immunosuppressive glioma microenvironment and limit the durability of immune-based therapies. In this review, we summarize how classical and metabolism-associated PTMs contribute to glioma immune evasion and immunotherapy resistance, highlight their potential as therapeutic entry points, and discuss the delivery, toxicity, redundancy, and heterogeneity barriers that must be addressed before PTM-directed strategies can be translated into effective combination therapies.</p>