Worldwide, there is a growing recognition that strategic partnering between cities and universities can bring substantial benefits for both sides. The big question is how to organize such partnerships successfully. This handbook offers insights, best practices and advice for leaders in cities and universities that want to go beyond “ad hoc” projects and take the next step towards a strategic and sustainable partnership. The handbook identifies promising avenues, but also barriers and pitfalls and how to avoid them. Illustrated by a rich variety of examples from European cities, the handbook provides concrete advice on the various stages of strategic city-university collaboration. This handbook intends to provide inspiring practices and guidance to develop strategic interaction between city and university, considering the complex and layered nature of both. The focus lies on the more strategic, transformational types of collaborations, that are more complex.