A new theoretical model was developed to predict the gas permeation behavior of mixed matrix membranes containing nanotubes (NT-MMMs). The proposed model was validated using a large number of CO2 /N-2 and CO2/CH4 separation data from the literature and a good agreement between the predicted and experimental data was observed. Most important, the proposed model explored the role of nanotube/matrix interface, by introducing the interfacial layer thickness parameter,l(int). Moreover, an excellent correlation between the l(int) values and nanotube/matrix interfacial interactions, obtained from thermodynamic theories, provides a guideline to design the interface layer for fabricating the NT-MMMs with desired gas separation properties, without any need to using the adjustable parameter. Moreover, the presented procedure is a good alternative approach to expensive and tedious traditional methods to estimate the interfacial layer thickness in polymer composites.