A CFD model was developed, covering a square area of 3.64 km2 and comprising the Holy Mosque near its center, the actual terrain, and the main buildings surrounding the Mosque. The gust wind effects on the existing cranes, the comfort of the pedestrians, and the air quality were studied for the first time in this Holy area. The air quality in this study was related to calm speed and creating a fertile environment for spreading infectious diseases. The study revealed that wind comfort levels are achieved in nearly all selected locations. Also, the wind speeds are generally low in the area. However, gusting wind currents appeared from limited directions, causing more wind loads on cranes. It is recommended to finalize some cranes' work shortly in specific locations or change their places, lower the crane boom at rest, and stop working on windy days. The air quality in some locations may be considered relatively poor. New tall buildings surrounding the Holy Mosque from the North and the East are not recommended except after studying their impacts on the air quality. Pruning North and/or East Mounts can remarkably improve natural ventilation. Large-scale fans are a solution after detailed study and simulation.