An interval programming optimization model was formulated to develop effective and feasible regional economic structure adjustment plan using Tangshan Municipality in China as a case study. The optimization model was coupled with a WRF-CAMx-PSAT air quality simulation system through the estimated industrial emission sensitivity coefficients and equivalent coefficients for PM2.5 concentrations. Seven categories of industries were examined, and the results indicated that industries with higher emission sensitivity coefficients should be given priority for control. The effectiveness of the obtained optimal schemes was further assessed by the air quality simulation system. It indicated that PM2.5 concentrations in Tangshan would decrease by [33.5%, 39.3%] than those in 2013. This study provided an effective method framework for industries to maximize profits while meeting certain air quality constraints under uncertainty through the coupling of air quality simulation and optimization models.