The requirements for the optimal building system design is numerous. However, most system designers do not take care of various design strategies. They often argue that the proper simulation tools are not existed to solve the implicated design requirements and the time to consider many alternatives of building systems are insufficient. The aim of this study is to develop the optimization interface program that considers various system design variables and eventually find both the optimal values of annual energy use and cost. Therefore, Doe2Opt is developed to easily perform simulation-optimization process based on DOE2 and GenOpt, and minimizes energy cost of small-to-medium sized building for 6.7% and that of large sized building for 3% with optimizing several HVAC system variables.