Large-scale desalinated water supply is increasingly being employed to mitigate water scarcity in arid regions. This alternative water source, while potentially reducing water shortage, has adverse environmental and social impacts, which should be considered at a project and regional scale if multiple projects exist. A methodological framework based on evidence from environmental impact studies is proposed to identify the main environmental and social concerns using the Atacama region in the north of Chile as a case study. This methodology incorporates project activities and receiving environment identification to understand the most significant impacts for a region, as well as a standardisation process to compare the findings from different environmental assessments. This methodology identifies the pressing environmental and social issues to guide a Strategic Environmental Assessment at a regional scale. Beyond the more recognised impacts of brine and energy consumption, our analysis identified impacts on terrestrial environments, principally affecting fauna, flora, and the cultural values of local communities, as primary concerns. This emphasis arises from the endemic nature of flora and fauna in arid regions and the often-irreversible nature of these impacts.