Fugitive emissions are one of the largest sources of volatile organic compounds (VOCs) from petrochemical and chemical plants. However, how to quantify the total fugitive VOC emissions from numerous and mostly inaccessible sources is a time consuming and costly task. This study presents a feasible approach to quantify the fugitive VOC emissions by integrating OPFTIR measurements and the well-developed Industrial Source Complex Short Term Model (ISCST3). A mobile OPFTIR system was set up for 190 hours in the downwind location of a 1,3-butadiene manufacturing process, which has unidentified fugitive sources and should be responsible for the elevated atmospheric 1,3-butadiene concentrations. Wind speeds and directions were found to be the most important factors in the dispersion of the emissions. Therefore, when using trial and error to predict the fugitive 1,3-butadiene emission rates, we divided the field measurement data based on the wind directions and excluded that obtained during lower wind speeds. Then the correlation coefficients between the field data (from the mobile OPFTIR system) and the modeling data (from the ISCST3) were found to be up to 0.529, and the slope of the correlation equation was close to unity. Therefore, integrating the OPFTIR measurement and ISCST3 is a feasible approach to predict the amount of fugitive VOC emissions.