This study, requested by the European Commission, addresses the challenge of multiple disciplinary interactions in Horizon 2020 projects, specifically in those with relevance to the Digital Agenda for Europe. It makes a series of recommendations that are aimed at improving the relevance, effectiveness, and appropriateness of multiple disciplinary interactions. The study is addressed to the European Commission, national research councils and other scientific funding agencies, the research community, and Horizon 2020 proposal evaluators and project reviewers. We show where interactions between disciplines add value to research and innovation projects. In doing so, we create a ‘smart approach’ to implementing multiple disciplinary interactions. Through this study, we invite the variety of actors involved in all elements of the Horizon 2020 research process to critically reflect on their own aspirations for the future of multiple disciplinary interactions in research.