With the publication of the European Green Deal, the European Union has committed to reaching carbon neutrality by 2050. The envisaged reductions of direct greenhouse gases emissions are seen as technically feasible, but if a wrong path is pursued, significant unintended impacts across borders, sectors, societies and ecosystems may follow. Without the insights gained from an impact assessment framework reaching beyond the techno-economic perspective, the pursuit of direct emission reductions may lead to counterproductive outcomes in the long run. We discuss the opportunities and challenges related to the creation and use of an integrated assessment framework built to inform the European Commission on the path to decarbonisation. The framework is peculiar in that it goes beyond existing ones in its scope, depth and cross-scale coverage, by use of numerous specialised models and case studies. We find challenges of consistency that can be overcome by linking modelling tools iteratively in some cases, harmonising modelling assumptions in others, comparing model outputs in others. We find the highest added value of the framework in additional insights it provides on the technical feasibility of decarbonisation pathways, on vulnerability aspects and on unintended environmental and health impacts on national and sub-national scale.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).