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 Es layer instability driven by the external dynamo currents are imposed into the potential equation to induce polarization electric fields for generating the MSTIDs. Simulations demonstrate that the MSTIDs alone can inhibit the upward growth of EPBs, but are insufficient to explain the disappearance of EPBs. The meridional winds are necessary to comprehend the underlying mechanism. The zonal and vertical E × B drifts of MSTIDs also affect the morphology of EPBs that could result in a reverse-C shape structure.