We foresee data-integrated simulation science growing into a challenging and influential research area in all fields of engineering and sciences that promises to have an enormous impact on many aspects of life. Its fundamental influence has already been argued for medicine, climate change, and in the context of smart manufacturing/Industry 4.0. We expect our methodological innovations to make their contribution to these fields. The Cluster will concentrate on selected engineering domains related to the research areas involving fluids, porous media, and biological matter in which the University of Stuttgart is particularly strong. All three examples draw on extensive preliminary research in EXC 310 and other collaborative projects, and they illustrate the necessary paradigm shift.