Atmospheric modeling is considered an important tool with several applications such as prediction of air pollution levels, air quality management, and environmental impact assessment studies. Therefore, evaluation studies must be continuously made, in order to improve the accuracy and the approaches of the air quality models. In the present work, an attempt is made to examine the air pollution model (TAPM) efficiency in simulating the surface meteorology, as well as the SO2 concentrations in a mountainous complex terrain industrial area. Three configurations under different circumstances, firstly with default datasets, secondly with data assimilation, and thirdly with updated land use, ran in order to investigate the surface meteorology for a 3-year period (2009–2011) and one configuration applied to predict SO2 concentration levels for the year of 2011.The modeled hourly averaged meteorological and SO2 concentration values were statistically compared with those from five monitoring stations across the domain to evaluate the model’s performance. Statistical measures showed that the surface temperature and relative humidity are predicted well in all three simulations, with index of agreement (IOA) higher than 0.94 and 0.70 correspondingly, in all monitoring sites, while an overprediction of extreme low temperature values is noted, with mountain altitudes to have an important role. However, the results also showed that the model’s performance is related to the configuration regarding the wind. TAPM default dataset predicted better the wind variables in the center of the simulation than in the boundaries, while improvement in the boundary horizontal winds implied the performance of TAPM with updated land use. TAPM assimilation predicted the wind variables fairly good in the whole domain with IOA higher than 0.83 for the wind speed and higher than 0.85 for the horizontal wind components. Finally, the SO2 concentrations were assessed by the model with IOA varied from 0.37 to 0.57, mostly dependent on the grid/monitoring station of the simulated domain. The present study can be used, with relevant adaptations, as a user guideline for future conducting simulations in mountainous complex terrain.