The “nexus” is a potentially very appropriate approach to enhance resource efficiency and good governance in transboundary basins. Until now, however, evidence has been confined to isolated case studies and the nexus approach remains largely undefined. The methodology presented in this paper, developed for preparing a series of nexus assessments of selected river basins under the Water Convention of the United Nations Economic Commission for Europe (UNECE), is a timely contribution to this ongoing debate. The nexus assessment of a transboundary basin has the objective of identifying trade-offs and impacts across sectors and countries and to propose possible policy measures and technical actions at national and transboundary levels to reduce intersectoral tensions. This is done jointly with policy makers and local experts. Compared to an Integrated Water Resource Management approach, the water energy food ecosystems nexus approach concurrently considers multiple sectors and their evolution. This offers the opportunity to better involve key economic sectors—energy and agriculture in particular—in the dialogue over transboundary water resource uses, protection and management.