A large number of organic contaminants are commonly found in industrial and municipal wastewaters. For proper unit design to remove contaminant mixtures by adsorption, multicomponent adsorption equilibrium models are necessary. The present work examined the applicability of Ideal Adsorbed Solution Theory (IAST), a prevailing thermodynamic model, and its derivatives, i.e., Segregated IAST (SIAST) and Real Adsorbed Solution Theory (RAST), to bisolute adsorption of organic compounds onto a hyper-cross-linked polystyrene resin, MN200. Both IAST and SIAST were found to be less accurate in fitting the experimental bisolute adsorption isotherms than RAST. RAST incorporated with an empirical four-parameter equation developed in this work can fit the adsorbed phase activity coefficients, γ, better than RAST combined with the Wilson equation or the Nonrandom two-liquid (NRTL) model. Moreover, two polyparameter linear free energy relationships were developed for the adsorption of a number of solutes at low concentrations in the presence of a major contaminant (4-methylphenol or nitrobenzene). Results show that these relationships have a great potential in predicting γ of solutes when the adsorbed amounts are dominated by a major contaminant. To the best of our knowledge, this is the first study predicting γ for bisolute adsorption based on molecular descriptors. Overall, our findings have proved a major step forward to accurately modeling multisolute adsorption equilibrium.