This study employs Computational Fluid Dynamics (CFD) to assess the impact of various ventilation configurations on respiratory droplet dispersion in a two-story restaurant building, aiming to reduce airborne infection transmission. A total of 24 scenarios, involving three ventilation configurations and eight individuals as potential droplet sources, are studied. The configurations—Case A, Case B, and Case C—are analyzed for their effectiveness in controlling droplet dispersion and improving air exchange effectiveness (AEE). Case B, with an outlet near occupants and an inlet above the zone separation, proved most effective in minimizing the droplet transmission between floors, reducing suspended airborne droplets on each floor, and preventing surface contamination, thereby enhancing indoor air quality. Despite the positioning inlet and outlet vents near crowded areas, Case A falls short in effectively removing droplets due to the intricate airflow patterns caused by air diffusers. Case C showed larger AEE but was less effective in droplet dispersion control, indicating a crucial balance between optimizing air circulation and limiting pathogen dispersion is needed. The findings underscore the importance of strategic ventilation design in mitigating airborne infection transmission in multi-level buildings. An optimal configuration, as demonstrated by Case B, combines efficient air distribution with strategic placement of ventilation components to create barriers against interzonal droplet transmission. This study highlights the potential of targeted ventilation strategies to significantly reduce the risk of airborne infection in enclosed, populated spaces.