Glioblastoma (GBM) is one of the most aggressive (grade IV) gliomas characterized by a high rate of recurrence, resistance to therapy and a grim survival prognosis. The long-awaited improvement in GBM patients'survival rates essentially depends on advances in the development of new therapeutic approaches. Recent preclinical studies show that nanoscale materials could greatlycontributetotheimprovementofdiagnosisandmanagementofbraincancers. Inthecurrent review, we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches. Moreover, we will summarize the main evidence for the potential of the IL-13R alpha 2 receptor (IL13a2R) targeting in GBM early diagnosis and experimental therapy.