Electronic (e)‐cigarette smoking is considered to be less harmful than traditional tobacco smoking because of the lack of a combustion process. However, e‐cigarettes have the potential to release harmful chemicals depending on the constituents of the vapor. To date, there has been significant evidence on the adverse health effects of e‐cigarette usage. However, what is less known are the impacts of the chemicals contained in exhaled air from an e‐cigarette smoker on indoor air quality, the second‐hand passive smoking of residents, and the toxicity of the exhaled air. In this study, we develop a comprehensive numerical model and computer‐simulated person to investigate the potential effects of e‐cigarette smoking on local tissue dosimetry and the deterioration of indoor air quality. We also conducted demonstrative numerical analyses for first‐hand and second‐hand e‐cigarette smoking in an indoor environment. To investigate local tissue dosimetry, we used newly developed physiologically based pharmacokinetic/toxicokinetic models that reproduce inhalation exposure by way of the respiratory tract and dermal exposure through the human skin surface. These models were integrated into the computer‐simulated person. Our numerical simulation results quantitatively demonstrated the potential impacts of e‐cigarette smoking in enclosed spaces on indoor air quality.