In this paper, an integrated model that coupled CONTAM and WUFI was developed to assess the indoor air quality (IAQ), moisture, and thermal comfort performance. The coupling method of CONTAM and WUFI is described based on the exchange of airflow rate control variables as infiltration, natural and mechanical ventilation parameters between heat and moisture flow balance equations in WUFI and contaminant flow balances equations in CONTAM. To evaluate the predictions of the integrated model compared to single models of CONTAM and WUFI, four scenarios were used. These scenarios are airtight-fan off, airtight-fan on, leaky-fan off, and leaky-fan on, and were defined for a three-story house subjected to three different climate conditions of Montreal, Vancouver, and Miami. The measures of the simulated indoor CO2, PM2.5, and VOCs obtained by CONTAM; the simulated indoor relative humidity (RH), predicted percentage of dissatisfied (PPD), and predicted mean vote (PMV) obtained by WUFI; and those obtained by the integrated model are compared separately for all scenarios in Montreal, Vancouver, and Miami. Finally, the optimal scenarios are selected. The simulated results of the optimal scenarios with the integrated model method (−28.88% to 46.39%) are different from those obtained with the single models. This is due to the inability of the single models to correct the airflow variables.