This paper addresses the simultaneous selection of solvents in the course of process synthesis. An integrated solvent and process selection framework is applied to the design of solvent-based separation systems and the design of reaction-/reactive extraction systems. The framework makes use of multi-objective optimisation to screen solvent candidates for non-inferior options with respect to properties impacting process design performance. Clustering techniques are then employed to effectively integrate solvent selection and process synthesis approaches. We address the implementation of the framework to the design complex systems with two applications. The first application demonstrates the use of the framework developing processing schemes for the separation of multi-component mixtures considering the combined use of different separation operations and solvent types. The second application addresses the selection of solvents and process configurations for ethanol production through fermentation and extraction. The applications illustrate how the framework supports the design engineer in selecting the optimum solvent-process options depending on requirements that combine process operating and economic as well as solvent performance considerations. Published by Elsevier B.V.