Recent studies of the TME of Ewing sarcoma, an aggressive fusion oncoprotein (EWSR1::FLI1)–driven primary bone tumor of adolescents and young adults (11–13), revealed the importance of extracellular matrix (ECM) remodeling (14) and hypoxia (15, 16) in promoting Ewing sarcoma tumor cell survival and metastatic potential. The gene discussed is FLI1; the disease is Ewing sarcoma.