In this study, by integrating three independent datasets, we revealed insights into the molecular behavior of GBM, particularly highlighting the roles of CD44, TNFSF14, and HOXD13. CD44 and TNFSF14 emerged as promising therapeutic targets in GBM due to their significant overexpression compared to normal brain tissue and their association with the ME subtype, which is linked to heightened inflammation, poorer prognosis, and immune suppression. Here, HOXD13 is linked to glioblastoma.