Process simulation software designs equipment, simulates operations, optimizes a plant's configuration (heat exchangers network, for example), estimates operating and capital expenses, and serves as an educational tool. However, mastering the theoretical background minimizes common mistakes such as applying an incorrect thermodynamic method, selecting improper algorithms in the case of tear systems, and setting irrational system specifications. Engineers and researchers will exploit this tool more often in the future as constant advancements in simulation science as well as new models are released continually. Process simulators make it easier to build digital twins and thus will facilitate the implementation of the industry 4.0 guidelines. We highlight the mathematical and technical features of process simulators, as well as the capabilities and the fields of application. A bibliometric map of keywords from articles citing Aspen+, Aspen plus, Hysys, and Pro/II indexed byWeb of Sciencebetween 2017 and 2020 identified the main research clusters, such as design, optimization, energy or exergy, biomass; H(2)and CO(2)capture, thermodynamics; and separations and techno-economic analysis.