Brain tumors are among the most devastating types of solid tumors to treat. Standard of care for glioblastoma (GBMs), the most aggressive form of primary brain tumors, has failed to improve the current survival rates in the past decades. Despite many other solid tumors, recent advances in cancer immunotherapies have also shown disappointing outcomes in GBMs. The heterogenous nature of GBMs, the immunosuppressive tumor microenvironment and the restrictive role of blood brain barrier (BBB) are some of the main challenges faced for treating GBMs. Electroporation-based treatments have demonstrated promising results, treating preclinical models of GBMs. It has been shown that low and high frequency irreversible electroporation treatments shift the immunosuppressive tumor microenvironment and reversibly open large areas of blood brain barrier (BBB). In this dissertation, in vitro cell culture models are utilized to study electroporation-based treatments for achieving a more optimized treatment for glioblastoma. We are proposing to utilize the immunomodulatory effects of electroporation treatments to improve the outcomes of immunotherapies in the brain. / Doctor of Philosophy / Despite the current advancements in treating solid tumors, brain tumors remain among the most difficult cancers to treat. The special structure of the brain as an organ as well as tumor complexity can lead to treatment failure. It is also known that infiltration of the immune cells within the tumor mass is limited due to the tumor's immunosuppressive nature. Hence, the use of newly advancing immunotherapy techniques is limited in the brain. Local treatments have become one of the most promising tools against brain tumors. Such treatments include methods that use excessive heating of the tissue to kill the tumors. Relying on heat for tissue destruction could damage the critical structures near the tumor and will reduce the favorable immune response after the treatment. A new treatment modality known as electroporation has been introduced for non-thermal treatment of brain tumors. Due to its non-thermal nature, electroporation treatments will allow for sparing of critical structures and can lead to a more robust immune response comparing to thermal treatment modalities. In this dissertation, we utilize electroporation-based treatments to try to overcome some of the challenges associated with treating brain tumors such as tumor heterogeneity and immune suppression.