This study is the first to investigate the performance of ultraviolet germicidal irradiation (UVGI) in underfloor air distribution (UFAD) systems. A simplified mathematical model is developed to predict airborne pathogen transport and inactivation by upper room UVGI in UFAD spaces. The proposed model is substantiated for the SARS-CoV-2 virus as a simulated pathogen through a comprehensive computational fluid dynamics methodology validated against published experimental data of upper room UVGI and UFAD flows. Simulations show an 11% decrease in viral concentration within the upper irradiated zone when a 15 Wlouvered germicidal lamp is utilized. Finally, a case study on Mycobacterium tuberculosis (M. tuberculosis) bacteria is carried out using the validated simplified model to optimize the use of return air and UVGI implementation, ensuring acceptable indoor air quality and enhanced energy efficiency. Results reveal that the UFAD-UVGI system may consume up to 13.6% less energy while keeping the occupants at acceptable levels of M. tuberculosis concentration and UV irradiance when operated with 26% return air and a UVGI output of 72W.