UPTAKE aims to facilitate the sustainable upscaling of carbon dioxide removal (CDR) methods by developing a set of robust strategies through technical, theoretical, and practical analysis accompanied by interactive dialogue within a CDR stakeholder forum. As a result, UPTAKE will develop a harmonised, comprehensive, inclusive, integrated, and transparent CDR knowledge inventory to evaluate a wide range of CDR technologies and methods, quantifying their national, European, and global costs, effectiveness, and removal potential as well as risks, constraints, and side-effects at different scales, and their prospects of technological progress. The UPTAKE approach will allow the assessment of geographical, sectoral, socioeconomic, demographic, and temporal trade-offs, co-benefits, and opportunities emerging from portfolios of different CDR methods. The enhanced socio-technical understanding of CDR methods will feed into an ensemble of state-of-the-art integrated assessment models (IAMs), which will help improve the integration of CDR methods given the EU policy objectives set for 2030, 2050, and beyond climate neutrality. UPTAKE will assess CDR governance and policy frameworks considering social acceptance, accountability, monitoring, and regulations for sustainable CDR rollout at scale. As a result, UPTAKE will generate an open and interactive CDR roadmap explorer to investigate strategies that are resilient to risks of failure and disruption, and minimise adverse impacts on society, economy, and the environment, aiming for a just, inclusive, and sustainable transition.