This research aims to close the practice-gap in the application of Design Thinking (DT) in complex, multi-stakeholder innovation ecosystem projects. The objective is to examine the challenges that businesses and policy-makers face when implementing DT practices in complex, inter-organisational innovation ecosystem projects; and to identify how these challenges can be overcome. The project outcomes offer strategic guidelines and tools to help businesses and policymakers advance the use of DT practices across organisational boundaries. The project operates at the intersection of design and innovation management practices: DT is increasingly acknowledged for its promise to help developing sustainable and profitable solutions to complex problems, enhancing organisational resilience, and reducing innovation risk, timescales and cost. However, limited empirical and conceptual evidence exists on the challenges emerging from practicing DT across organisational boundaries. Empirically, this research adopts a comparative case-study approach to examine six complex multi-stakeholder innovation projects in Germany and the United Kingdom.