In a centralized air distribution system, the designed ductwork layout impacts the system performance and the construction time and cost. Engineers face various challenges, including spatial limitations, leading them to use assumption-based design methods to balance their design with construction requirements. As a result of this shortcoming, insufficient design details for construction and improper coordination between designers and trade workers will occur, increasing the project duration and risk for conflicts. As the construction industry shifts towards off-site and fast-paced construction methods, the design processes must comply with construction requirements to ensure a smooth transition from conventional methods to off-site construction. This research provides a scientific and systematic method for design and optimization of the HVAC air distribution system in terms of the ductwork layouts, and sizes and types of ducts to standardize the construction processes for time and cost reduction in the off-site environment. The proposed methodology utilizes Building Information Modeling for coordination of the air distribution system using a 3D database. Furthermore, a trained genetic algorithm processes the data and identifies alternative solutions. As the final step, the algorithm generates the optimal air distribution system in the BIM 3D environment for a visual assessment and detailing. The results are verified based on existing case studies in the Canadian prefabricated, panelized construction company. The potential benefits include 23% savings in duct material, whilst providing an integrated design solution with 32% less conflicts comparing to traditional design methods.