Significance Oxygen heterogeneity in solid tumors is recognized as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal tumor vascular structure. We investigate the role that anomalies in red blood cell transport plays in establishing oxygen heterogeneity in tumor tissue. We introduce a metric to characterize tumor vasculature (mean vessel length-to-diameter ratio, λ ) and demonstrate how it predicts tissue-oxygen heterogeneity. We also report an increase in λ following treatment with the antiangiogenic agent DC101. Together, we propose λ as an effective way of monitoring the action of antiangiogenic agents and a proxy measure of oxygen heterogeneity in tumor tissue. Unraveling the causal relationship between tumor vascular structure and tissue oxygenation will pave the way for new personalized therapeutic approaches.