Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant brain tumor that usually affects very young children and typically causes death, despite very aggressive treatment. The biological properties contributing to tumor aggressiveness and resistance to common chemotherapeutic agents are currently unknown. Previous studies have shown the activation of Insulin like growth factor-I receptor (IGF-1R) in ATRT tumor specimens and cell lines. Additionally, angiogenesis is an established physiological mechanism that supports the survival and progression of brain tumors. Vascular endothelial growth factor receptor (VEGFR) signaling pathway is a major regulator of angiogenesis in brain tumors. We hypothesized that molecular interactions may exist between these two signaling pathways. Our findings show evidence for a novel IGF-1R/VEGFR-2 cross-talk in response to IGF-I mediated activation. Furthermore, we show evidence that the inhibition of IGF-1R/VEGFR-2 pathways by the small molecule inhibitors lead inhibition of cell migration properties and the initiation of apoptosis. Overall, the data generated in this set of studies present a framework to evaluate and utilize the receptor cross talk pathways to identify novel treatment approaches for ATRT in the future.