This textbook collects the lecture notes of the Course of "Separation Unit Operations and Process Simulation", with the aim to provide an effective tool to learn and develop a technical expertise about this topic at industrial level. The book discusses the fundamentals about process simulation and process simulators, the calculation of thermodynamic properties, and the best methods available in commercial process simulators. Then, thermal separation processes (i.e. flash, quench and multi-stage distillation) as well as non-thermal separation processes (absorption, stripping, and solvent extraction) are addressed. The procedures for design and rating calculations of separation columns (both diameter and height), with reference also to construction details are eventually presented.