At a time of system shocks, significant underlying challenges are revealed in current approaches to delivering infrastructure, including that infrastructure users in many societies feel distant from nature. We set out a research agenda on systems approaches to infrastructure, drawing on ten years of interdisciplinary work on operating infrastructure, infrastructure interventions and lifecycles. Research insights and directions on complexity, systems integration, data-driven systems engineering, infrastructure life-cycles, and the transition towards zero pollution are summarised. This work identifies a need to better understand the natural and societal impacts of infrastructure interventions under uncertainty. We argue for a change in current approaches to infrastructure: starting from the natural environment and its resources, encompassing societal use of infrastructure and the supporting infrastructure assets and services. To support such proposed new systems approaches to infrastructure, researchers need to develop novel modelling methods, forms of model integration, and multi-criteria indicators.