Two-phase partitioning bioreactors (TPPBs) support the removal of volatile organic compounds (VOCs) from contaminated gaseous emissions at unprecedented rates and concentrations. TPPBs are biological multiphase systems provided with a non-aqueous phase (NAP) with high affinity for the target VOC. Although modeling of TPPBs is a research field that has rapidly evolved, recent experimental findings such as the direct VOC uptake from liquid NAPs and the quantification of simultaneous partial mass transfer coefficients have not been incorporated yet in a comprehensive mathematical description. In this work, a mathematical description of TPPBs, including continuous aqueous phase renewal and potential VOC uptake directly from the NAP, was developed. Model simulations indicated that TPPB performance can be enhanced by improving the partial mass transfer coefficient between the gas and the NAP (by increasing the contact between the gas and the NAP). The model also showed that microorganisms with half-saturation constants < 5 g m-3 and ability to take up VOC directly from the NAP can boost significantly TPPB performance. The present modeling platformwas tested against experimental data from literature for methane, hexane and dichloromethane and no parameter fitting was carried out.