Pediatric brain tumors are a significant concern, representing the most common solid tumors and a leading cause of cancer-related deaths in children. These tumors exhibit considerable heterogeneity, encompassing a wide range of distinct neoplasms with differences in their developmental origins, genomic profiles, treatment approaches, and patient outcomes. Despite advancements in diagnosis and treatment that have improved survival rates and quality of life for many children, the prognosis remains unfavorable, and current treatments often lead to significant long-term consequences. Moreover, therapeutic innovation for brain tumors faces unique challenges due to the intricacies of the brain, the prevalence of side effects, and the presence of the blood-brain barrier (BBB). The lack of effective technologies for delivering drugs across the BBB also hampers pharmaceutical targeting of the central nervous system (CNS). In this chapter, we explore various strategies designed to address the challenges the BBB poses. We begin by examining existing treatment options and their limitations. Subsequently, we delve into methods for overcoming the BBB, representing a significant breakthrough in immunotherapy for pediatric brain tumors.