Energy loss and performance deterioration caused by the stack effect are emerging issues in high-rise office buildings (HROB). However, a single countermeasure may not completely remove the stack effect problems, so combinations of countermeasures are often considered in building commissioning or retrofit projects to achieve the desired results. Therefore, a comprehensive study on combinations is necessary for the final decision-making. In this study, a multi-criteria decision-making model is proposed, which is utilized to calculate the ranking of countermeasure combinations for the final decision-making index by assigning weights and conducting comprehensive analysis on four criteria: infiltration energy loss, maximum pressure difference, investment cost, and implementation resistance. Based on a two-level Fractional-Factorial design (FFD), the interaction effects between countermeasures were verified, and the regression models of infiltration energy loss and maximum pressure difference were obtained as well. The investment cost and implementation resistance were defined according to the investigation and survey. An Analytic Hierarchy Process (AHP) was applied to establish the weights of each criterion. A weighted Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method was applied to establish the decision-making index. Through the case study of a HROB located in northern China, it was concluded that the ideal combination can reduce infiltration and pressure difference by 26.88% and 87.58%, respectively, with low-level investment costs and implementation resistance. The results indicate that the multi-criteria model provides a comprehensive ranking of countermeasure combinations, which can serve as a quantitative basis for the final decision-making. Furthermore, this multi-criteria decision-making approach can be extended to other buildings in other regions.