There is an abundance of actions that could positively change the way food systems operate in the Mediterranean region. However, the uptake of these actions at local level has proven to be slow and often limited in their scope and impact. Considering the diverse nature of agri-food systems challenges in the region, trade-offs in interventions and the diversity of stakeholders, a radical shift from focusing on top-down, global solutions for sustainable food systems, to adapting demand driven, country-led actions is required. This review uses a food systems lens to identify four levers which are essential to “enable” and accelerate the adoption of game changing solutions to food systems challenges by local actors in the Mediterranean region. These are namely: 1) Multi-stakeholder collaboration; 2) Data and evidence; 3) Technological innovation; and 4) Coherent policies and investment. We recognize that each of these enablers is a powerful mean of change, but the evidence suggests that a sustainable and inclusive transformation is only possible when they are deployed together in an integrated and inten-tional way. Results of this review outline some of the barriers to unlocking the potential of enablers and provide insights on how to use their power to transform Mediterranean food systems.