Central nervous system tumors remain the leading cause of cancer-related morbidity and mortality in pediatric patients. Despite the progress made over the past years on understanding the cellular and molecular interactions inside the tumor and the addition of targeted drugs against several genetic or biological features, many children still fail to respond to the therapy. With new advances in single cell technologies, an increasing number of studies have pointed out a marked intra-tumor heterogeneity landscape of brain tumors in adults and its direct relationship with cancer development and maintenance. Nonetheless, less progress has been made in understanding the molecular underpinnings of this disease in children. Profiling the transcriptome of individual cancer and tumor-associated immune cells will drive a better understanding of the tumor heterogeneity which will help in the discovery of druggable targets and the designing of specific treatment protocols based on the needs of each child. Through the use of single-cell RNA sequencing, we expect to provide insight about brain tumor heterogeneity and its influence in progression and response to therapy.