Rivers, as powerful natural agents, have historically been not only sources of life and sustenance but also the creators and connectors of culture. From ancient civilizations that shaped agricultural lands and built their cities along riverbanks to the modern landscapes that have developed around them, rivers have always been central to the identity, sustainability, and evolution of human societies. The Menderes (Maeander) River in southwestern Anatolia presents a unique case of how a river can shape both natural and cultural landscapes. This river basin, often called the "Valley of Civilizations”, has played a crucial role in settlement development and cultural shaping throughout Anatolia's history. As the landscape evolved, its water-related relationships—marked by the river's fluctuating presence, scarcity, and abundance—have given rise to new heritage forms, further complicating management of this multi-layered landscape. Addressing this complexity requires a heritage information management and decision support system capable of integrating multi-scale, multi-faceted data for sustainable management. In this regard, Geographic Information Systems (GIS) have proven to be valuable tools, creating comprehensive, interdisciplinary platforms to understand, analyze, and manage diverse layers of complex landscapes. Thereupon, MeRiΔGIS, a GIS-based heritage information management and decision support system, is established to understand and assess the multi-dimensional characteristics of the Menderes River Delta for its conservation and sustainable management. MeRiΔGIS provides a comprehensive understanding of the ongoing transformations in the riverine landscape, emphasizing the interaction between natural and cultural components, as well as the key human and more-than-human agents shaping its evolution. Ultimately, the MeRiΔGIS serves as a tool to re-establish fragmented relationships between the river, its surrounding communities, and the landscape. This interdisciplinary, GIS-based approach offers a model for managing other riverine and water-linked landscapes, integrating heritage conservation with modern information management technologies to address the complexities of the natural-cultural nexus.