Diffuse midline gliomas, H3 K27-altered (DMG) are highly aggressive malignancies of the central nervous system that affect both pediatric and adult populations. The immune layout and genetic changes within the tumor microenvironment associated with these high-grade malignancies are thought to play an integral role in the phenotypic differences in tumor presentation and clinical outcomes between both populations. It is suspected that these differences may play a role in future treatments for DMG and further research is needed to explore this.