As one of the largest agglomerations of cities in the world, the infrastructure and living conditions of the residents in the Pearl River Delta (PRD) have significantly improved since the late 1970s. However, as a two-sided sword, the boosting of economic growth has inevitably exerted adverse effects on the environment in this region. To further understand the current fine particulate matter (PM2.5) pollution sources in this region and formulate an effective future air pollution control strategy for it, a hybrid source apportionment method was applied to adjust source estimates of secondary inorganic aerosols (SIAs) [particulate sulfate (SO42−), nitrate (NO3−), and ammonium (NH4+)] by combining Comprehensive Air Quality Model Extensions and measurement data from 19 sampling sites covering the PRD region in 2015. After correction by the hybrid method, the normalized mean errors for the three major species SO42−, NO3−, and NH4+ in PM2.5 simulated by the model decreased from 0.412, 1.261, and 0.401 to 0.321, 0.565, and 0.130, respectively. Tianhu, Taishan, Taipa Grande, whose secondary inorganic aerosol concentration variations are −48.33%, −40.59%, and 39.10% after adjustment, respectively, are the three top sites with the most substantial modification. Our study revealed that the emissions outside the PRD region are still the most important contributor to the three components after the correction. In most Hong Kong sites, the adjusted mobile source is subordinate to the cross-boundary transport and became the largest endogenous source.In contrast to that in Hong Kong, preceded only by super-regional sources, the outstanding contributor to SIAs in Guangdong and Macao is the area source. Our results indicated that besides collaborative control measures, the Hong Kong and Guangdong government should emphasize the emissions from motor vehicles and residential sources, respectively. Overall, this hybrid source apportionment approach can narrow down the discrepancy between simulation results and observational data. Thus, it is a potentially reliable method to provide a more solid theoretical foundation for formulating air pollution control measures.