This paper presents a new methodology which employs physicochemical properties and their relationships to separation techniques for design and synthesis of separation processes. The methodology covers a wide range of separation problems and consists of selection and identification of separation techniques (and the corresponding separation tasks), the sequencing of the separation tasks and the determination of appropriate and consistent conditions of operation. For a specified multicomponent separation problem, subsets of feasible separation techniques are first identified for every binary and user-specified separation tasks. The number of alternatives for each separation task is reduced by systematically analyzing the relationships between properties, separation technique and conditions of operation. After the final step, an estimate of the final process flowsheet is produced with a list of possible alternatives for the separation tasks. Application of the methodology is demonstrated through examples highlighting the different steps of the methodology.