Pediatric brain tumors present significant clinical challenges due to their diverse subtypes and complex genomic profiles. This study aimed to elucidate the genomic landscape of these tumors to better understand their biology and identify potential therapeutic targets. We analyzed 400 pediatric brain tumor cases, revealing a predominant occurrence of medulloblastomas (30.0%), followed by pilocytic astrocytomas and ependymomas. Key findings include high frequencies of MYC amplification in medulloblastomas (33.3%), BRAF mutations in pilocytic astrocytomas (75.0%), and C11orf95-RELA fusions in ependymomas (66.7%). Therapeutic targets were notably prevalent in specific subtypes, suggesting actionable opportunities for personalized treatment. Survival analysis indicated that genomic alterations, such as MYC amplification and IDH1/2 mutations, significantly impact patient prognosis. These results enhance our understanding of tumor-specific molecular mechanisms and support the development of targeted therapies, addressing the need for more effective treatments in pediatric brain tumors.