Abstract Cities are nowadays faced with an unprecedented crisis, due above all to the impacts of climate change and the increasing social inequalities, which require innovative approaches and more effective tools. Resilience is widely interpreted as a key principle to re-frame urban policies, paving the way to cross-sectoral urban strategies capable of better coping with contemporary challenges. This contribution focuses in particular on the 100 Resilient Cities (100RC) Initiative, launched by the Rockefeller Foundation and addressed to support cities all over the world in developing and implementing strategies capable of increasing urban resilience in the face of multiple shocks and stresses, including climate change. In detail, based on the comparative analysis of two case studies, Rome and Athens, this paper aims at providing insights on the main strengths and weaknesses of cities’ resilience-building processes developed under the 100RC Initiative and at deeply analyzing the contribution of the delivered Resilience Strategies to the improvement of cities’ capacities to cope with contemporary challenges and above all with the increasing impacts of climate change.