Office buildings are significant contributors to energy consumption and carbon emissions due to high occupancy density and prolonged operation. To balance decarbonization with indoor environmental quality, this study proposes a simulation-driven multi-strategy optimization framework for a three-story office building in Jinan. This study integrates EnergyPlus 23.2, jEPlus+EA 2.3.2, and the NSGA-II algorithm to co-optimize building performance. We evaluate the synergistic effects of roof photovoltaic coverage ratio, night ventilation turn-on temperature difference, and HVAC control strategies on carbon emissions and thermal comfort, while ensuring that CO₂ concentrations remain within health thresholds. The results indicate that the night ventilation temperature turn-on temperature difference is the most influential parameter. It yields standardized regression coefficients (SRCs) of 0.7456 for carbon emissions and 0.5325 for thermal discomfort. The Pareto-optimal solution achieves a carbon footprint of approximately 477 tCO₂, with only 8.8% indoor discomfort hours. This framework provides a robust, practical approach for the low-carbon and healthy operation of office buildings.