The development of static real-time control systems often follows a closed-world assumption, allowing extensive RTOS-aware whole-program optimization. For single-core systems, previous work could show the high potential of control-flow-aware static system-call tailoring. However, due to an exponential state explosion in the analysis phase, it cannot simply be extended to a multi-core setting, since the core’s relative timing to each other is undetermined. In this work, we present MultiSSE, a multi-core capable and RTOS-aware static whole-system optimization. First, MultiSSE analyzes the system by determining the relative positions of multiple cores only when necessary. For that, it exploits structural control flow and optionally timing information to handle each core separately as much as possible. Based on the analysis result, a synthesis applies lock elision and system-call optimization to generate specialized multi-core real-time systems for AUTOSAR OS. To enable a static prediction of the run-time reduction, we additionally provide cost models for the optimized cross-core system calls and evaluate the approach with synthetic benchmarks and a real-world quadrotor application. MultiSSE was able to optimize or even completely elide costly cross-core system calls and system objects leading to a reduction of up to 14% of a task’s execution time. In this extended version of a conference publication (Entrup et al. 2023), we provide an advanced description, new cost models, and an end-to-end measurement by developing a synthesis complementing the analysis.