Anticipating and managing future regional climate risks in interconnected multi-sectoral systems is complicated by uncertainties in risk drivers within both human and natural systems. Comprehensive yet comprehensible targeted climate risk information exploring these uncertainties is essential for tasks like the strategic allocation of limited resources to vulnerable areas and sectors in the region. To address these complexities, this study introduces an interdisciplinary methodology combining meteorological, hydrological, and socio-economic perspectives, tested within the flood-prone, transboundary Lielupe basin shared by Latvia and Lithuania. A ’plausibilistic’ risk assessment approach is applied in which plausible climate scenario storylines are sampled based on their relevance for local impacts, allowing the assessment of conditional changes in high-impact probabilistic discharges. In addition, we sampled plausible socio-economic storylines to asses future urban area and economic sectoral development. This information allows us to project the impact potential in the region and its cascading socio-economic effects. By integrating both socio-economic and climate scenario storylines, our approach comprehensively maps complex direct and cascading flood risks. Application to the Lielupe basin highlights sub-catchments and sectors consistently vulnerable across the diverse, relevant, and credible set of future storylines. Our integrated approach equips regional risk managers with targeted and robust risk information, providing a strong knowledge base for prioritising adaptation planning.