Unsteady separated flow from deployed weapons bay doors can interact with the highly unsteady flow in the open bay cavity, which is known to exhibit strong acoustic content and could lead to fluid-resonance and high-intensity acoustic noise. The culmination of these unique flow physics can potentially excite structural modes of the doors, aircraft surfaces, or externally carried munitions and fuel tanks and can ultimately lead to aeroelastic instabilities, such as buffet, flutter, limit-cycle oscillations, or fatigue-induced failures. A hybrid Reynolds-averaged Navier–Stokes large eddy simulation (RANS/LES) method with low-dissipation schemes is developed to improve flow and acoustics predictive capabilities for supersonic weapons bays. Computational simulations are conducted for a weapons cavity with different deployed bay doors configurations, including the effect of dynamically moving doors, to assess the tonal content and unsteady aerodynamic loads on the doors. Wind tunnel testing is also carried out to provide unsteady experimental data for use in validating the high-fidelity simulation capability. The simulation results in terms of unsteady pressure, velocity fluctuations, and pressure resonant frequencies are computed and presented. The results suggest that the deployed doors energize the shear layer and cause it to go deeper into the cavity and produce higher unsteady fluctuations on the weapons cavity floor and aft wall. The deployed doors also cause a shift in the dominant resonant modes.