Politicians usually ask science to provide evidence to support their decisions. Nowadays, global scenarios are addressing complex socio-economic systems, where a diversity of variables and stakeholders are deeply and often indirectly entangled. This complexity does not allow to provide accurate and long term predictions for the evolution of the scenarios and the impacts of decisions. In this context, trans-national relations are struggling with the dynamics of the systems which can show undesired asymmetric shocks or fast instabilities. “Science, measured against reality, is primitive and childlike -- and yet it is the most precious thing we have”. Despite evidence and experience could be not enough, the awareness of the potential and limits of a knowledge-based support for the collection of events, their analysis and provision of option assessments is definitely useful. In a scientific approach to solutions to challenges, the process which can enable the system to achieve them, has to be appropriately designed and structures. This mainly implies that, within the complexity of the actual world, the governance for the decision process and implementation of actions has to fit the purpose, in such a way to identify the essential roles and competences. Often, the requests of representativeness, legitimacy, credibility and accountability of the different aspects involved in the governance are too complicated respect to what really needed, introducing other levels of complexity which introduce delays, increase of costs, lack of focus. The governance should be therefore adopted following the principles of networks, analyzing the economy of scale of its ecosystem: time, space and energy (or entropy) are fundamental to make the system efficient and effective, especially when dealing with multi-lateral and multi-level relations.