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The automotive industry is experiencing a significant transformation driven by the demand for automation, autonomy and resource reduction. A key factor in this transformation is the model-based design and validation of advanced vehicle systems, particularly Steer-by-Wire systems, which are essential for highly automated and autonomous vehicles. However, Steer-by-Wire systems, characterized by the absence of a mechanical connection between the steering wheel and the front wheels, present unique challenges for achieving robust control as well as ensuring driving comfort and safety. This dissertation addresses these challenges by exploring innovative approaches for the optimal control of Steer-by-Wire systems, highlighting the model-based design and the integration of simulation environments. For this, a detailed model is developed, considering all relevant degrees of freedom and nonlinear characteristics of a real Steer-by-Wire system. Based on this detailed model, the dissertation presents a novel multivariable control approach that enhances the robustness and performance of Steer-by-Wire systems compared to traditional designs. The derived control approach demonstrates improved system stability and performance, effectively addressing parameter uncertainties and varying driving conditions. These satisfactory characteristics are validated both in an augmented simulation environment and on a real prototype. By combining virtual testing within the augmented simulation environment with real-world prototyping, the need for labor-intensive physical testing is minimized, thus optimizing development resources and time. The presented methods are not only employed for the development of Steer-by-Wire systems, but also for further applications in automotive engineering, including driver assistance systems, sensor evaluations and perception systems. In conclusion, the research contributes to mechatronics and automotive engineering by advancing autonomous driving through robust control approaches, virtual testing and agile development strategies. The insights and methodologies proposed not only advance the development of novel Steer-by-Wire systems, but can also serve as a basis for future innovations in mechatronic systems that require precise control and reliability.