System simulation is a part of the overall field of systems engineering and provides quantitative results to verify and validate the architecture and parameters of a system under development. In the meantime, system simulation is a wellestablished activity in the automotive development area and covers a broad range of applications over the whole development process from system architecture definition, component dimensioning up to virtual testing and calibration. In all of these steps, simulation helps the systems engineer find the best choice of system architectures, evaluate the component target characteristics, define the control logic and parameters, and support the individual tests. Thanks to system simulation, proper system function can be confirmed in early phases of development, which minimizes the number of cost-intensive development loops. In addition, verification and validation and calibration tasks can be frontloaded to reduce overall development time. This chapter focuses on the setup of different physical domain models and how they are linked together. The modeling approaches of the individual domains and simulation management are discussed.