Residential energy efficiency and ventilation retrofits (eg, building weatherization, local exhaust ventilation, HVAC filtration) can influence indoor air quality (IAQ) and occupant health, but these measures' impact varies by occupant activity. In this study, we used the multizone airflow and IAQ analysis program CONTAM to simulate the impacts of energy retrofits on indoor concentrations of PM and NO in a low-income multifamily housing complex in Boston, Massachusetts (USA). We evaluated the differential impact of residential activities, such as low- and high-emission cooking, cigarette smoking, and window opening, on IAQ across two seasons. We found that a comprehensive package of energy and ventilation retrofits was resilient to a range of occupant activities, while less holistic approaches without ventilation improvements led to increases in indoor PM or NO for some populations. In general, homes with simulated concentration increases included those with heavy cooking and no local exhaust ventilation, and smoking homes without HVAC filtration. Our analytical framework can be used to identify energy-efficient home interventions with indoor retrofit resiliency (ie, those that provide IAQ benefits regardless of occupant activity), as well as less resilient retrofits that can be coupled with behavioral interventions (eg, smoking cessation) to provide cost-effective, widespread benefits.