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Integrated Care Systems (ICSs) were created across the English National Health Service (NHS) to foster collaboration between health and care organisations within 42 geographical footprints. They were established, in part, to address significant financial and operational challenges, which had only intensified by the time ICSs became statutory bodies in 2022. 1–3 Thus, ICSs find themselves attempting to foster collaboration amidst intense system turbulence, which is liable to undermine such efforts. Deemed ‘the makings of a sensible management structure’ by Lord Darzi’s recent review of the English NHS, ICSs show no signs of going away.4 Accordingly, this commentary outlines a research agenda to explore whether and how ICSs can effectively collaborate in this turbulent context and to support them in these efforts. This problem-driven research agenda does address leadership issues, but not exclusively, also calling for research on how ICSs can navigate competing goals and manage power within their systems.