The health perspective in urban science brings new methodological challenges to planning of city networks. Due to the system of systems nature of healthcare, new methods are needed to facilitate disciplinary integration and management of models and models-of-models. Participation of stakeholders and policy makers demands the uptake of new methods and a new perspective on the use of interfaces and boundary objects. In this chapter, the authors discuss evidence from five projects that use gaming, simulation, modeling, and data analytics in unconventional ways for design of large-scale urban systems to provide a methodological path forward for overcoming traditional engineering approach issues.