Although a variety of modeling tools have been developed to predict potential public exposure to harmful transportation emissions at regional and sub-regional scales, computational efficiency remains a critical concern in the design of modeling tools. Microscale dispersion models run at high resolution and require extremely long runtimes for larger roadway networks and high-resolution receptor grids. Motivated by the challenges encountered in the previous modeling efforts, this work develops an advanced modeling framework for region-wide applications of line source dispersion models that integrates a high-performance emission rate lookup system (i.e., MOVES-Matrix), link screening, and innovative receptor site selection routines to further accelerate model implementation within distributed computing modeling framework. The case study in the 20-county metropolitan Atlanta area accounts for an extremely large number of link-receptor pairs demonstrates that the modeling system generates comparable concentration estimates to extremely-high-resolution processes, but with very high computational efficiency. The comprehensive modeling methodology presented in this work will make comparison of air quality impacts across complex project scenarios (and transportation development alternatives over large geographic areas) much more feasible. All these aspects should be of interest to a broad readership engaged in near-road air quality modeling for transportation planning and air quality conformity and for environmental analysis under the National Environmental Policy Act.