The objective of this research is to investigate how to replace human decision-making with computational intelligence at a scale not possible before and in applications such as manufacturing, transportation, power-systems and bio-sensors. The approach is to build upon recent contributions in algorithmic motion planning, sensor networks and other fields so as to identify general solutions for planning and coordination in networks of cyber-physical systems. The intellectual merit of the project lies in defining a planning framework, which integrates simulation to utilize its predictive capabilities, and focuses on safety issues in real-time planning problems. The framework is extended to asynchronous coordination by utilizing distributed constraint optimization protocols and dealing with inconsistent state estimates among networked agents. Thus, the project addresses the frequent lack of well-behaved mathematical models for complex systems, the challenges of dynamic and partially-observable environments, and the difficulties in synchronizing and maintaining a unified, global world state estimate for multiple devices over a large-scale network. The broader impact involves the development and dissemination of new algorithms and open-source software. Research outcomes will be integrated to teaching efforts and undergraduate students will be involved in research. Underrepresented groups will be encouraged to participate, along with students from the Davidson Academy of Nevada, a free public high school for gifted students. At a societal level, this project will contribute towards achieving flexible manufacturing floors, automating the transportation infrastructure, autonomously delivering drugs to patients and mitigating cascading failures of the power network. Collaboration with domain experts will assist in realizing this impact.