Climate chambers enable repeatable indoor boundary conditions and are increasingly used to study multi-domain IEQ. However, thermal comfort and IAQ are still often evaluated separately, limiting evidence on their coupled behavior and potential trade-offs under different ventilation and air-cleaning strategies. The present study was carried out in the climate chamber located in the laboratory facilities of the University of Western Macedonia to quantify thermal comfort and IAQ simultaneously across different experimental scenarios that vary ventilation mode, heating operation, and occupancy. The results show a correlation between subjective and objective measurements, with the comfort temperature varying around 22.2 °C, as estimated by the Griffiths model, while ventilation mainly affects the stability of the thermal environment. CO₂ levels scaled with occupancy and ventilation rate, while PM removal was strongly strategy-dependent: after a controlled smoke event, mechanical ventilation plus air purification achieved the fastest decay and recovery toward near-background concentrations. Overall, this work represents a first step toward coupled IEQ research by jointly quantifying thermal comfort and IAQ in a climate chamber, enabling systematic comparison of ventilation strategies in terms of both perceived comfort and pollutant exposure.