Estimation of the activities or solubility of small molecules in polymers is essential in a number of process applications such as the mixture separation by polymeric membrane, polymeric membrane preparation, polymer preparation, especially, the selection of membrane material for a predefined separation process. The VTPR EoS-G(E) group contribution model has been used to predict the activities of water, alkane, and aromatic small molecules in poly(vinyl alcohol), poly(dimethyl siloxane), and polyisobutylene polymeric membrane materials. The influence of temperature and the molar mass of polymer on the activities of small molecules in the polymeric membrane are discussed. It has been shown that the results predicted by the VTPR EoS-G(E) model are good agreement with the experimental ones, and the total average deviation between the experimental and the calculated is no more than 3%. It should be expected that the VTPR EoS-G(E) group contribution model could be applied to the polymeric membrane material selection, to the polymeric membrane preparation processes and to the polymeric material preparation processes.