This is the last in a series of three reports that explore how science was mobilised in response to the COVID-19 pandemic. The report focuses on system-level issues and highlights challenges and opportunities that are inherent to the organisation of science systems and that need to be addressed to improve the resilience of these systems and their capacity to address complex societal challenges and crises. The analysis is structured around five interconnected themes: the strategic mobilisation of science capacity; managing conflicting priorities; co-ordination and collaboration across levels of governance; transdisciplinary and reflexive science; and dynamic and system-oriented governance. Key areas for intervention and more specific policy actions are identified under each theme and provide a framework for systemic action to strengthen science in support of socio-technological transitions.