Brain tumors are the leading cause of cancer‐related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient‐derived organoids (PDOs) from ependymomas, medulloblastomas, low‐grade glial tumors, and patient‐derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine. Synopsis Patient‐derived organoids (PDOs) and patient‐derived xenograft organoids (PDXOs) have been established through direct in vitro culture of primary tumors and patient‐derived xenograft (PDX)‐derived tumors with the goal to better model pediatric tumors of the central nervous system. PDOs recapitulate cellular heterogeneity, histological features, mutational profiles (number of variants, microsatellite instability, tumor mutational burden) of the corresponding parental tumor even after 1 year of in vitro culture ZFTA‐RELA EPN‐ and G3 MB‐PDOs recapitulate patients' response to routinely applied therapeutic regimens Several PDOs and PDXOs were derived from human tumors for which there are currently very limited in vivo and in vitro models available PDOs and PDXOs are available to the research community, and can be subjected to genetic manipulations, to drug screening, and translational applications for personalized medicine Patient‐derived organoids (PDOs) and patient‐derived xenograft organoids (PDXOs) have been established through direct in vitro culture of primary tumors and patient‐derived xenograft (PDX)‐derived tumors with the goal to better model pediatric tumors of the central nervous system.