A pioneering study demonstrates that extracts from the human amniotic membrane (hAME) significantly potentiate the anti-cancer efficacy of doxorubicin in neuroblastoma cells by impeding angiogenesis and tumor progression pathways. These findings reveal that the combination therapy suppresses neovascularization via modulation of the PHD-2/HIF-1α axis, addressing a key mechanism limiting chemotherapy success. This multimodal approach offers promising therapeutic advantages in pediatric oncology by targeting tumor vascularization and enhancing drug potency with potential for reduced systemic toxicity.