A thermodynamic framework is presented for modeling combined ion-exchange and molecular adsorption phenomena at a solid-liquid interface. The analysis of the uptake of both ionic and molecular species by the solid surface is based on the concept of exchange reactions. The adsorption model is coupled with a previously developed comprehensive thermodynamic speciation model for the aqueous phase. A parameter regression procedure is developed that decouples the determination of equilibrium constants from the evaluation of activity coefficients for the adsorbed phase. The model is applied to analyze the behavior of an aqueous aniline system in contact with a clay material saturated with calcium. In this system, an ion-exchange reaction between anilinium and calcium ions takes place simultaneously with the adsorption of neutral aniline molecules. The combined adsorption and speciation model is also used for analyzing the coupling of solid solubility and ion exchange in a system that contains a phosphate rock and a clinoptilolite mineral loaded with a mixture of potassium and ammonium ions. For all investigated systems, good agreement with experimental data is obtained.