The increasing reliance on computer and communication technologies exposes control systems to cyber security threats. The physical systems can now be attacked through cyberspace. Emerging sophisticated attacks can exploit zero-day vulnerabilities, persist in the system for long periods of time, and advance stealthily to achieve their attack goals. Protection and prevention against such attacks are not always possible, and a paradigm shift to emphasize resilience of a control system is the overarching objective for safeguarding control systems to protect nation's critical infrastructures. The major challenge for designing secure and resilient cyber-physical control system is the lack of scientific foundations, and quantitative methods to provide a systematic guideline for large-scale cyber-physical interactions. To this end, the project aims to establish a meta-game system theory, and develop computational and design methodologies for cyber-physical co-design problems. Game-theoretic tools serve as an appropriate way to interconnect systems from multiple domains into one single framework to address security and resilience issues of highly integrated CPS. This project investigates a meta-game framework as a new paradigm to compose heterogeneous system components to design their interactions to achieve functional security and resiliency properties. Through developing security-aware controllers and impact-aware proactive cyber defense mechanism, this project creates a system co-design paradigm based on the meta-game framework, which captures the system properties of robustness, security, and resilience in one single framework, and provides fundamental principles to characterize their tradeoffs. The analytical framework will lead to the development of a cyber-physical mechanism design theory to provide a solid foundation for achieving optimal cyber-physical integration for control systems. The developed analytical and design tools will allow the prediction of unexpected outcomes of system integrations, the mitigation of the impact of cyber attacks on control systems, and the cost-effective operation and design of resilient CPS.