Therapeutic efficacy of chemotherapy is highly dependent on the ability to deliver drug molecules across tissue and cellular barriers. Ultrasound stimulated microbubbles (USMB) have been shown to enhance the delivery and cytotoxicity of various classes of chemotherapeutic agents. Here, the application of USMB in combination with the chemotherapeutic class vinca alkaloids is investigated. Specifically, vinorelbine tartrate (VRL) and vinblastine sulfate (VBL) of the vinca alkaloid class, which to the best of our knowledge have not been reported in combination with USMB, were used in this study. Cell viability analysis demonstrated that USMB does not enhance the cytotoxicity of either drug. VRL+USMB showed to have an additive response in cell death, whereas VBL+USMB resulted in an additive effect at a low peak negative pressure, and antagonistic at higher pressures. This work suggests that the mechanism of uptake is an important factor in determining the effectiveness of a chemotherapy drug with USMB treatment.