Health and care systems in Europe are facing core common challenges, which require harmonised and coordinated solutions. The European Partnership on Transforming Health and Care Systems (THCS) represents a unique strategic opportunity to bring together stakeholders, create synergies, coordinate Research and Innovation actions, facilitate the digitization of health and care services and support the transformation of health and care systems with innovative solutions driven by knowledge and evidence. The general objective of THCS is to contribute to the transition towards more sustainable, efficient, resilient, inclusive, innovative and high-quality people centred health and care systems equally accessible to all people. For this purpose, THCS aims not only to create new knowledge and scientific evidence but to co-design new solutions and support their transfer and scale-up across countries and regions while also fostering capacity building. The approach for a successful and smooth implementation of THCS will focus on three main work streams: 1) Filling the knowledge gaps with research actions aiming at providing the necessary evidence, 2) Implementation and transfer aiming at supporting actions focusing on the testing of existing solutions and adaptability in different national and regional contexts, and 3) Boosting health and care systems through dedicated activities (capacity building and trainings, study visits, technical assistance, twinning, networking) involving different health and care stakeholders. To address these three work streams, THCS is built around four pillars that group different types of activities addressing different types of stakeholders of the health and care system. The activities are organised in ten Work Packages working closely together to achieve the objectives of the Partnership and clustered in the four Pillars.