The recent deterioration of Taiwan's air quality is partly due to fine particulate matter (PM2.5). With several studies pointing out a direct link between PM2.5 and the global disease burden, plans are underway to reach the standard of an annual average PM2.5 concentration of 15 µg m–3 in Taiwan by 2020. Subsequently, environmental protection bureaus in all cities should assess PM2.5 emission sources and implement control strategies. This study focuses on analysis of PM2.5 sources within Tainan City in an effort establish the contribution of large-scale pollution sources within the city as well as those from neighboring counties and cities. During this study, the top nine largest emission sources in Tainan City were investigated: (1) the Chemical manufacturing industry, (2) the iron and steel industry, (3) the power industry, (4) manufacturing of coal-based products, (5) diesel vehicles, (6) two-stroke scooters, (7) catering, (8) construction/road dust, and (9) open burning. Three important pollution sources in the central region of Taiwan were investigated as well, including: (1) the Taichung Power Plant, (2) the Formosa Petrochemical Corporation (FPCC) Sixth Naphtha Cracking Industry, and (3) the Dragon Steel Company in Taichung City, Changhua County, and Yunlin County, respectively, all of which are located on the windward side of Tainan City. The Community Multiscale Air Quality Model (CMAQ) was used to simulate the impact of the mentioned sources on Tainan’s air quality. The results for the monthly contributions from the different sources averaged over a one year period indicated that diesel vehicles are the largest source, emitting up to 1.06 µg m–3, followed by the Taichung Power Plant, which had 0.87 µg m–3 the construction industry and road dust emissions, with 0.80 µg m–3, and with open burning of waste having the lowest contribution. These results can be applied to facilitate the development of follow-up air quality control strategies.