How to best assess potential health, environmental and other impacts of genetically modified organisms (GMOs) and how to interpret the resulting evidence base have been long-standing controversial issues in the EU. As a response, transparency and inclusiveness became a major focus of regulatory science activities in the GMO impact area. Nevertheless, nearly three decades of controversies resulted in a heavily polarized policy environment, calling for further efforts. Against this backdrop the EU funded project GRACE explored the value of evidence synthesis approaches for GMO impact assessment and developed an evidence synthesis framework with a strong emphasis on openness, stakeholder engagement, transparency, and responsiveness to tackle regulatory science challenges. This framework was tested and implemented in the course of 14 systematic reviews or maps conducted on selected review questions spanning potential health, environmental, and socioeconomic impacts of GMOs. An inclusive development and prioritisation of review questions is of key importance in evidence synthesis as it helps to provide a better link between stakeholder demands and concerns and policy relevant outcomes. This paper, therefore, places a particular focus on the stakeholder involvement strategy developed and experiences gathered during this particular step in the course of the GRACE project. Based on this experience, possible lessons for future engagement exercises in highly controversial fields of regulatory science are discussed.