A simple molecular thermodynamic model, based on the QSPR/LSER approach, is presented. The development involves a critical examination of the suitability of available LSER molecular descriptors for calculations of properties of pure-component bulk phases, concentrated solutions, and interfaces. The appropriate descriptors for these calculations are obtained by applying simple and straightforward criteria on freely available data for pure compounds. These criteria arise from a re-examination of basic elements of the solvation picture on which the LSER approach resides. Extensive tables with molecular descriptors are reported. The predictive capacity of the model is tested against a variety of experimental data for mixtures including vapor-liquid equilibria, drug solubilities, and wetting behavior of solid polymer surfaces. Emphasis is given on hydrogen-bonded mixtures. The results are rather satisfactory, in view of the breadth of applications and the nonuse of adjustable parameters. All working equations are expressed in terms of LSER descriptors. The strength and weakness of the model are also critically discussed along with the perspectives of this unified approach to mixture thermodynamics.