Osteosarcoma is characterized by extensive chromosomal instability and highly heterogeneous genomic alterations. Leveraging a large osteosarcoma genomic cohort and a pan‐cancer reference population, this study identifies age‐associated patterns of genomic alteration across pediatric, adolescent, and young adult patients. The findings provide a new framework for understanding osteosarcoma heterogeneity and support future efforts to refine molecular classification, patient stratification, and genome‐informed therapeutic development.