Despite obstacles, institutional barriers and prejudices, interdisciplinarity is a growing movement within academia. Evolving from the pioneering experiences in broad multidisciplinary ventures since the post–Second World War era, interdisciplinary programmes and research projects are now a worldwide reality in universities. Complex and interconnected challenges of humanity, such as social unrests, economic and ecological crises, political turmoil and global human health emergencies demand integration of efforts and competencies of researchers from a wide range of backgrounds, and the involvement of actors from outside the academia. In recent years, complex challenges fuelling the need for better integration of work in universities and research centres with real demands of societies are further feeding transdisciplinary endeavours. Such movements pose new questions, ranging from institutional arrangements to methodological frameworks, which are far from being solved. This article reflects on the nature and practice of scholarly engagement in this trajectory during the 21st century from vantage points of the Global South. Some insights are based on what we have learnt over our work lives, and some are based on collected information about experiences in India and Brazil. This contribution also raises questions that could potentially concern other countries, especially in the Global South. However, it is not a handbook directly applicable to realities other than Brazil and India. Discussions in academia about pathways to interdisciplinarity should go beyond its legitimisation. The agenda now has to shift towards transdisciplinary co-construction of knowledge, by creating gateways to connect the scientific world to the ‘real world’.