Pediatric central nervous system (CNS) tumors pose a significant challenge in pediatric oncology, as they are the leading cause of cancer-related mortality among children. To address this critical issue, the development of reliable animal models that accurately replicate pediatric tumorigenesis is essential for advancing therapeutic strategies. This chapter outlines refined techniques for stereotactic intracranial injection models that reproduce exact anatomical locations and crucial immune characteristics of a tumor, thereby enabling robust assessments of immunotherapy efficacy in age-appropriate murine systems. Moreover, these models are vital tools for the preclinical evaluation of therapeutic interventions targeting the tumor immune microenvironment. We provide a detailed examination of the implantation modalities used for various tumor types, including injections into the cortex, cerebellum, fourth ventricle, and pons. The precision of these injections is imperative for accurately modeling tumor growth and the associated immune responses within these distinct brain regions. Ultimately, our comprehensive protocol serves as a methodological framework for preclinical studies of pediatric brain tumors, facilitating rigorous evaluations of therapeutic approaches in orthotopic murine models.