Nosocomial transmission of airborne pathogens remains a persistent threat in multi-bed hospital wards. This study quantifies how personalized exhaust devices, combined with the main two-bed patient room ventilation, can suppress cross-contamination and contributes a configuration-spanning assessment that links personalized exhaust operating set-points to removal efficacy across six layouts, providing design guidance absent from prior single-layout studies. A three-dimensional hospital ward was solved with the Reynolds-Averaged Navier–Stokes (RNG k-ε). At the same time, particle trajectories representing pathogen-laden aerosols were computed by one-way-coupled Discrete Phase Modeling augmented with a Discrete Random Walk stochastic dispersion scheme. Six different ventilation layouts were combined with personalized exhaust flow rates of 0 (off),10, 20, and 40 L/s. Two infection scenarios were simulated: (i) one infectious patient served as the particle source, while a second patient and a healthcare worker were modeled as susceptible targets; (ii) both patients were infectious, with the healthcare worker being the target for exposure. Ventilation geometry strongly governed room airflow and particle transport; without personalized exhaust, inhalation fractions differed by an order of magnitude between layouts. Activating personalized exhaust at 20 L/s reduced inhalation fractions by ≥ 80% in half of the layouts, while 40 L/s achieved complete particle removal in all configurations. In the dual-infection scenario, simultaneous operation of both personalized exhaust units at 20 L/s diminished healthcare-worker exposure by 75%. These results demonstrate that personalized exhaust devices provide robust, configuration-independent mitigation of aerosol transmission and should be considered a complementary strategy to conventional ward ventilation.