NetZero Energy Homes (NZEHs) have emerged as a solution to alleviate the energy demand from residential building operation, where appropriate design of building envelope and mechanical system is a means to achieving energy conservation and recovery for NZEHs. This research thus proposes an informed decision making framework for NZEH building design based on an automated energy simulation approach. The Batch Version of HOT2000 is utilized to achieve automated single-factor and combined-factor simulations, and a total of 16 200 combinations of building envelope and mechanical device design options are simulated for NZEH design. An NZEH project in Edmonton, Canada, is utilized as the case study in this research. The initial design of the NZEH results in an estimated energy deficit of 6048.0 MJ, accounting for 8.8% of the total consumption, and, based on the combined-factor simulations results, improved design scenarios are recommended for this NZEH. The simulation results of the initial design are also validated using the monitored data, with the actual performance showing an energy deficit of 4.1% of total consumption. Furthermore, such analysis as regression, factor importance ranking, and temperature set-point simulation are also conducted for the NZEH building design. This research proposes a framework to support informed design decision making for NZEHs, and builds a baseline for future study.