Starships – or interstellar craft – are considered the next major leap in the exploration of the Cosmos by mankind. Currently starship development is in its infancy due to the lack of a practical and adequate propulsion technology. If we consider manned interstellar travel the challenge is even more complex, and also shifts towards creating a fully autonomous system that is resilient over a long period of time. In fact a starship can be considered as the ultimate model for closed, autonomous systems, and as such has functional applicability in creating a more sustainable Earth. Traditionally, space systems design is being guided by incorporating as many contingencies as possible, and then training and anticipating for that. However, because of the sheer scale and inherent unpredictability of an interstellar mission, this approach cannot be relied upon any longer. A fundamentally different design paradigm is needed. Any manned space architecture that is geared towards long-term exploration needs to address the needs of three core systems: the technical, social and ecological system. This study proposes the merging of those three systems into one participatory system as a key strategy to deal with uncertain futures. This merging is achieved through the application of three interrelated design principles: (1) radical integration, (2) evolvability, and (3) co-creation. The proposed design paradigm is informed by a series of art/science projects in which technical, social and ecological systems are explicitly merged. Through a Living Labs analysis the internal dynamics of these projects are disentangled and described. The three design principles naturally emerge out of this analysis. Consequently the repercussions of applying these design principles on space systems design are explored through a series of simulations. The HI-SEAS Mars simulation entailed a 4-month isolation experiment with a crew of 6 participants. Results drawn from this study are complemented by agent-based modeling. A virtual simulation of evolvable starship architectures explores the concept of embedding evolution into space systems. Finally overall conclusions are drawn on how the proposed design paradigm could lead to mission success during deep space exploration.