In Heating Ventilating and Air Conditioning (HVAC) systems, ventilation strategies impact building energy consumption, occupants’ thermal comfort and Indoor Air Quality (IAQ). Ventilation strategies such as Mixing Jet Ventilation (MJV), Displacement Ventilation (DV), and Impinging Jet Ventilation (IJV) are operated on the different principals. MJV relies on dilution, while DV and IJV rely on both dilution and stratification. Due to climatic variation, ventilation strategies must be operated under different cooling and heating load scenarios. Typically, each ventilation strategy controls the indoor environment through a single adequate flow rate with suitable supply parameters such as temperature, pollutant concentration, vapor, velocity, etc. Hence, the indoor thermal and IAQ condition are independently impacted. A room with excellent thermal condition is possible to have poor IAQ. Given this limitation, vast air flow variables, and occupants’ activities, the performances evaluation of these strategies are complicated. In this study, three ventilation strategies, MJV, DV, and IJV are thoroughly investigated. The Computational Fluid Dynamics (CFD) simulation was mainly utilized to handle the complexity of this study. The parametric studies of 48 CFD simulations are presented. Referring to ASHRAE RP-1133, the experimental data from a specially built HVAC-IEQ laboratory was used to validate the CFD data. The research results indicate both advantages and disadvantages in all three strategies. In addition, there is no single strategy that can perform excellently in all indexes. Using the well-known index called ventilation effectiveness (VEF), DV performs outstandingly. However, under a newly proposed index called ventilation performances, DV fails because the stratification discomfort exceeds 36% of room area. MJV suffers from low VEF and excessive draft. However, the IAQ of MJV is not as poor as expected. IJV can be an alternative especially for space where sleeping and sitting activities dominate. IJV can conserve HVAC energy, while maintaining good IAQ. Compared to DV, although VEF is lower, stratification discomfort is minimized to 24%–12% (depending on supply velocity). Overall, this study demonstrates that ventilation strategies are the key to enhance IAQ. Therefore, the utilization of an appropriate ventilation strategy might increase, Leadership in Energy and Environmental Design (LEED) score, particularly for Indoor Environmental Quality, Innovation and Design Process, and Energy and Atmospheric categories.