Research aimed at contributing to the further development of integrated water resources management needs to tackle complex challenges at the interface of nature and society. A case study in the Cuvelai-Etosha Basin in Namibia has shown how semi-arid conditions coinciding with high population density and urbanisation present a risk to people’s livelihoods and ecosystem health. In order to increase water security and promote sustainable water management, there is a requirement for problem-oriented research approaches combined with a new way of thinking about water in order to generate evidence-based, adapted solutions. Transdisciplinary research in particular addresses this issue by focusing on the problems that arise when society interacts with nature. This article presents the implementation of a transdisciplinary research approach in the above-mentioned case study. The concept of social-ecological systems (SES) plays a key role in operationalising the transdisciplinary research process. Application of the SES concept helps to outline the problem by defining the epistemic object, as well as structure the research process itself in terms of formulating research questions and developing the research design. It is argued here that the SES concept is not merely useful, but also necessary for guiding transdisciplinary sustainability research and implementation. The study from Namibia clearly demonstrates that the introduction of technological innovations such as rainwater and floodwater harvesting plants requires a social-ecological perspective. In particular this means considering questions around knowledge, practices and institutions related to water resources management and includes various societal innovations alongside technologies on the agenda.