Temozolomide is easily the most broadly used chemotherapy for patients with glioblastoma (GBM) even though roughly 1 / 2 of treated patients have temozolomide resistance and all sorts of patients eventually fail therapy. Because of the limited effectiveness of existing therapies, immunotherapy has been broadly investigated for patients with GBM. However, initial immunotherapy trials in GBM patients have experienced disappointing results as monotherapy. Therefore, combinatorial treatment strategies are now being investigated. Temozolomide has lots of effects around the defense mechanisms which are determined by mode of delivery and also the dosing strategy, who have unpredicted effects on immunotherapy. Ideas summarize the immune modulating role of temozolomide alone and in conjunction with immunotherapies for example dendritic cell vaccines, T-cell therapy, and immune checkpoint inhibitors for patients with GBM.