GUARDEN’s main mission is to safeguard biodiversity and its contributions to people by bringing them at the forefront of policy and decision-making. This will be achieved through the development of user-oriented Decision Support Applications (DSAs), and leveraging on Multi-Stakeholder Partnerships (MSPs). They will take into account policy and management objectives and priorities across sectors and scales, build consensus to tackle data gaps, analytical uncertainties or conflicting objectives, and assess options to implement adaptive transformative change. To do so, GUARDEN will make use of a suite of methods and tools using Deep Learning, Earth Observation, and hybrid modelling to augment the amount of standardized and geo-localized biodiversity data, build-up a new generation of predictive models of biodiversity and ecosystem status indicators under multiple pressures (human and climate), and propose a set of complementary ecological indicators likely to be incorporated into local management and policy. The GUARDEN approach will be applied at sectoral case studies involving end users and stakeholders through Multi-Stakeholder Partnerships, and addressing critical cross-sectoral challenges (at the nexus of biodiversity and deployment of energy/transport infrastructure, agriculture, and coastal urban development). Thus, the GUARDEN DSAs shall help stakeholders engaged in the challenge to improve their holistic understanding of ecosystem functioning, biodiversity loss and its drivers and explore the potential ecological and societal impacts of alternative decisions. Upon the acquisition of this new knowledge and evidence, the DSAs will help end-users not only navigate but also (re-)shape the policy landscape to make informed all-encompassing decisions through cross-sectoral integration.