During the last few decades, building designs for all kinds of high occupancy spaces, such as hotels, shopping centers, hospitals, stadia, and airport terminals have undergone significant changes, in order to meet the ever-increasing demand for efficiency, comfort and safety in case of emergencies in larger and ever more complex projects. Computational Fluid Dynamics (CFD) simulations have proven to be a flexible and effective numerical tool for developing, optimizing and validating tailored solutions in increasingly complex and demanding projects. At Dar Al- Handasah (Shair and Partners), an architecture and engineering design firm founded in 1956, and a pioneering force in the planning, design and implementation of development projects in the Middle East, Africa and Asia, these CFD simulations are extensively used at an early phase in the design process to support the design. Indeed, simulations are used as an optimization and validation tool to develop innovative designs incorporating energy-saving and safety measures geared toward decreasing the overall facility's energy costs, while improving occupant comfort and safety. This paper will showcase the use of CFD simulations using ANSYS FLUENT in the design and optimization of Heating, Ventilation, and Air-Conditioning (HVAC), and smoke management systems for a typical high-ceilinged and high-density assembly space. Specifically, the simulations are used to predict local conditions, such as flow field, temperature and relative humidity distributions and optimize HVAC design parameters, such as supply air flow and size/distribution of outlets to maintain a comfortable thermal environment in normal mode of operation. In case of an emergency fire event, the simulations will help visualize the spread of smoke and optimize the emergency ventilation parameters to avoid causalities and ensure the safe evacuation of occupants in compliance with applicable international fire and life safety codes.