The 45th edition of SafeComp, to be held in Valencia, Spain, provides a unique occasion to explore and debate the growing challenges of safety-critical computing systems. Safety is more relevant than ever, as adaptive and advanced digital infrastructures are increasingly embedded across all layers of hardware and software, giving rise to complex systems of systems. These computing systems must not only deliver high performance and scalability but also work in a sustainable way, addressing energy efficiency, resource usage, and long-term societal impact.