Climate change and accelerating socioeconomic developments increasingly challenge flood-risk management in the Vietnamese Mekong River Delta—a typical large, economically dynamic and highly vulnerable delta. This study identifies and addresses the emerging challenges for flood-risk management. Furthermore, we identify and analyse response solutions, focusing on meaningful configurations of the individual solutions and how they can be tailored to specific challenges using expert surveys, content analysis techniques and statistical inferences. Our findings show that the challenges for flood-risk management are diverse, but critical challenges predominantly arise from the current governance and institutional settings. The top-three challenges include weak collaboration, conflicting management objectives and low responsiveness to new issues. We identified 114 reported solutions and developed six flood management strategies that are tailored to specific challenges. We conclude that the current technology-centric flood management approach is insufficient given the rapid socioecological changes. This approach therefore should be adapted towards a more balanced management configuration where technical and infrastructural measures are combined with institutional and governance resolutions. Insights from this study contribute to the emerging repertoire of contemporary flood management solutions, especially through their configurations and tailoring to specific challenges.