The Long-Term Vision for the Schelde estuary was determined as “the development of a healthy and multifunctional estuarine water system that can be utilized in a sustainable way for human needs.” This Dutch–Flemish managerial plan sets quality targets for the condition of the estuary by the year 2030 and the management measures to achieve them. Targets were developed and integrated from three central perspectives: accessibility of the ports, safety against floods in the densely populated catchment, and ecosystem health. This study focuses on the ecological rehabilitation of the estuary and the creation of sustainable nature, seeking possible alliances with security measures against floods, navigation requisites for port activities, and enhancement of the estuary's educational and recreational values. The estuary and its valley were subdivided into ecologically relevant zones. Key parameters were identified, and a conceptual rehabilitation model was developed, based on a problem analysis. Goals were set in a semiquantified way for most attributes of the estuarine functioning and prioritized for each zone. Rehabilitation measures with maximal contribution to the priority goals were identified for each zone. Spatial analysis of the study area indicated optimal areas for the implementation of these measures. To exemplify the array of possibilities on an ecosystem level, two different rehabilitation plans were proposed, each from a different approach. The potential contribution to the rehabilitation of the estuary was compared for both alternatives.