To assess the impact on indoor air quality (IAQ) of products with the potential to reduce individual risk and population harm in comparison to smoking cigarettes, an environmentally controlled exposure room was built in Philip Morris International Research & Development facility. An analytical platform, including 11 online and offline methods, was developed, validated, and subsequently applied for several studies involving volunteer panelists. It has long been known that the presence of human beings and their daily activities in an enclosed environment can significantly modify IAQ by releasing several hundreds of volatile organic compounds from breath and skin. We evaluated the impact of panelists present in the exposure room for two hours and also of different common human activities (drinking wine, using cosmetics, and cooking) during so-called “activity sessions.” Each activity was assessed separately using our analytical platform and exposure room under controlled environmental conditions. One method in particular, which is part of the analytical platform, measures the total volatile organic compounds (TVOC) yield and main contributors within a given range of volatility present in air. Its measurement relies on the use of gas chromatographic instrumentation equipped with parallel mass spectrometry and flame ionization detectors, allowing simultaneous quantification and identification of compounds present in the room atmosphere. The results obtained by TVOC analysis showed that prolonged human presence as well as indoor activities led to a deterioration of IAQ. Moreover, it was shown that TVOC patterns would vary qualitatively and quantitatively depending on the activities. Few constituents were specific for a type of experiment (e.g., fusel alcohols for the wine session), while most had just different patterns of increase (e.g., methylcyclosiloxanes had highest concentration in the cosmetic session). These learnings were applied to optimize the design for IAQ studies.