Scientists and engineers have been constructing models of complex phenomena for centuries. Computational simulation helps us understand important aspects of the systems described, predict system states under different conditions, and derive decisions for controlling them. Simulation technology has become an indispensable tool for research, development, and operations in many different areas. Much of the technological progess in our modern society depends on continual advances in the field of simulation. Since 2019, the Cluster of Excellence EXC 2075 "Data-Integrated Simulation Science" which is embedded into the Stuttgart Center for Simulation Science will pose a multitude of novel research challenges over the next decade. It will address the relevance of insights and knowledge obtailable from the abundance of data from sensors, digitized collections, experiments, and simulations.