Since Venus has no substantial planetary magnetic field, the fast‐flowing solar wind plasma interacts directly with its ionosphere, upper atmosphere, and corona. The thermal atmosphere and hot oxygen corona of Venus are expected to play essential roles in the interaction process. To quantify their effects, we combine three major state‐of‐the‐art three‐dimensional numerical models, including (a) The Venus thermosphere general circulation model (VTGCM), (b) The adaptive mesh particle simulator (AMPS), and (c) A multi‐species Magnetohydrodynamics (MHD) model of Venus based on Block Adaptive Tree Solar‐wind Roe Upwind Scheme. The global multi‐species MHD model is used to simulate the planet's interaction with the ambient solar wind, where the background neutral densities are provided by VTGCM and AMPS. Using the above‐mentioned numerical models, the effect of the upper atmosphere and corona on solar wind driven ion escape rates are examined for three typical solar cycle conditions, including solar maximum, solar median, and solar minimum conditions. The model results suggest that even though the hot oxygen corona only has a minor effect on the ion density profiles in the ionosphere, it can enhance ion loss rate up to ∼25% for high solar activity. Key Points An advanced magnetohydrodynamics model is used to quantify the effects of the neutral atmosphere of Venus on the solar wind interaction process Realistic 3D neutral atmospheres change ion densities in the upper ionosphere and the ion loss rates for different solar activities The hot oxygen corona significantly increases the total ion loss rate under solar maximum conditions