This report has been prepared as part of the Lagging Regions project of the JRC. In the 2021-2027 programming period, smart specialisation strategies will be required to meet a series of fulfilment criteria around the relevant "enabling condition" of good governance. One such criterion relates to international collaboration, or measures for enhancing cooperation with partners in different countries in areas designated as priority areas for smart specialisation. The potential for Lagging Regions to participate in interregional and international cooperation remains under-exploited, and this report determines specific challenges as well as potential benefits and opportunities that are relevant for low-growth and low-income regions. An exploration of interregional and international cooperation aims to contribute to a better understanding of its role in strengthening innovation ecosystems and its interaction with Smart Specialisation in the context of Lagging Regions.