We assessed the chronic health risks from inhalation exposure to volatile organic compounds (VOCs) and particulate matter (PM2.5) in U.S. offices, schools, grocery, and other retail stores and evaluated how chronic health risks were affected by changes in ventilation rates and air filtration efficiency. Representative concentrations of VOCs and PM2.5 were obtained from available data. Using a mass balance model, changes in exposure to VOCs and PM2.5 were predicted if ventilation rate were to increase or decrease by a factor of two, and if higher efficiency air filters were used. Indoor concentrations were compared to health guidelines to estimate percentage exceedances. The estimated chronic health risks associated with VOC and PM2.5 exposures in these buildings were low relative to the risks from exposures in homes. Chronic health risks were driven primarily by exposures to PM2.5 that were evaluated using disease incidence of mortality, chronic bronchitis, and non-fatal stroke. The leading cancer risk factor was exposure to formaldehyde. Using disability-adjusted life years (DALYs) to account for both cancer and non-cancer effects, results suggest that increasing ventilation alone is ineffective at reducing chronic health burdens. Other strategies, such as pollutant source control and the use of particle filtration, should also be considered.