This study was carried out to provide support to the Impact Assessment of Horizon Europe, the European Framework Programme for Research and Innovation (2021-2027). The socio-economic and environmental impacts were assessed against the baseline of continuation of the Horizon 2020 Programme (2014-2020) for different policy options distinguishing: management options (centralised or decentralised), budgetary options (increase or decrease of budget) and general design options (clustered into two groups aiming at “More Impact” and “More Openness”). This assessment was conducted using the NEMESIS macro-economic model, which allows to translate R&D investments and the related knowledge spillovers into endogenous growth mechanisms.