Use of volumetric contrast-enhanced ultrasound (US) imaging of cancer-bearing mice allows description of whole tumor perfusion and monitoring response to drug treatment. Thirty mice were implanted with breast cancer cells. Following sufficient tumor growth, mice were sorted into four treatment groups: Abraxane, TRA-8, Abraxane + TRA-8, or control. Mice were administered drug treatment on days 0, 3, 7, 10, 14, and 17. Whole tumor contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before drug dosing. At termination, tumors were excised and immunohistologic analyses were performed. Therapeutic efficacy was detected within 7 days after drug dosing with volumetric contrast-enhanced US imaging. The most significant reduction in tumor perfusion as compared to control mice measurements was observed in the TRA-8 + Abraxane dosed animals (P = 0.001). The reduction in perfusion observed in the TRA-8 + Abraxane group coincided with a reduction in tumor size during the same time period. Survival curves illustrate that combination TRA-8 + Abraxane improves drug efficacy compared to monotherapy. Overall, preliminary results demonstrate that volumetric contrast-enhanced US imaging of changes in whole tumor perfusion levels allows early monitoring of cancer response to drug therapy.