A wise integration approach using well-developed and innovative existing scientific/engineering tools can be a good answer to rising core questions of sustainability science. Many research works have been conducted to protect and satisfy occupant health and comfort in a sustainable way. The present study investigates a novel approach to the control of ventilation, dynamically integrated with the use of air cleaning technology toward a substantial reduction of building energy/cost with cleaner indoor air than what the standard provides. To demonstrate the proposed methodology, a low energy office building was used as a testbed, subject to the variation of outdoor pollution due to nearby traffic. A detailed building model was constructed by utilizing DesignBuilder and ContamW based on the building design/actual construction documents for the analyses of combined IAQ and energy benefits. Target contaminants included formaldehyde, other 16 representative VOCs and CO2 for IAQ analysis. Dynamic profiles of outdoor pollution were based on actual monitoring data and EPA 2008 AirData. By setting up a suite of usage scenarios under four representative climate and outdoor air quality conditions throughout the U.S. including Syracuse (cool), Los Angeles (mild), Houston (cooling dominant) and Duluth (heating dominant), the approach of dynamic integration of ventilation and air cleaning was assessed. Results showed that the minimum ventilation rate requirements in ASHRAE 62.1-2010 might not be sufficient for meeting the exposure limit constraints for IAQ (especially for formaldehyde) at all times. The integration strategy would provide satisfactory IAQ, and also could bring most energy/cost benefits (∼11% annual savings) for the case building.