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This chapter describes the transition from single-helix roadmap innovation to Open Innovation 2.0 (OI 2.0), based on Quadruple Helix innovation processes. Innovation is intended to make things happen in new and better ways, but actual take-up is always an essential aspect of successful innovation. A change of mindset to be in accord with the behaviour and processes in innovation ecosystems is crucial for an understanding of the interdependencies and complexity management that lead to impact. OI 2.0 is a ‘mash-up’ parallel process in which the public policy maker needs to create a safe framework for this interaction (mash-up) to take place. OI 2.0 is genuinely intersectional, as innovation increasingly happens at the crossroads of technologies and applications – it is not the linear extrapolation of the past. To speed up scalability, all stakeholders need to co-create solutions and find innovations together in real-world settings. Only then do we have a strong driver to create new markets and services and scale up successes rapidly: There is inherent buy-in in this kind of innovation environment. At the same time, by involving end users as co-creators up front and seamlessly, less successful experiments and failing prototypes are rapidly revealed as such: ‘failing fast, scaling fast’ is one of the strongest advantages of OI 2.0. All this leads to the Quadruple Helix innovation model, which supplements the Triple Helix model (research, industry, public sector) with the additional component of the people. In the Quadruple Helix, citizens are not the passive objects of new products or services but active agents contributing to the whole innovation process.