The Naval Research Laboratory first-principles ionosphere model SAMI3/ESF is performed to study the interaction between the nighttime medium-scale traveling ionospheric disturbances (MSTIDs) and equatorial plasma bubbles (EPBs). The synthetic dynamo currents are imposed into the potential equation to induce polarization electric fields for generating the MSTIDs. Simulations demonstrate that the MSTIDscan inhibit the upward growth of EPBs; however, MSTIDs alone are insufficient to explain the disappearance of EPBs. We found that the meridional winds likely contribute to the disappearance of MSTIDs by reducing the background electron density and polarization electric fields within the EPBs. Then, the MSTIDs transport plasma to fill the EPB depletions up via E × B drifts. Both MSTIDs and meridional winds are necessary to comprehend the underlying mechanism of EPB disappearance. Additionally, we also found that the zonal and vertical E × B drifts within the MSTIDs affect the morphology of EPBs, leading to a reverse-C shape structure.