The 15-month coordination and support action “4.UNCAN.eu” will generate a strategic agenda to launch UNCAN.eu, a European initiative to UNderstand CANcer proposed by the Mission Board and the European Beating Cancer Plan. This research agenda will be built with the final aim of achieving a new breakthrough in cancer prevention and treatment that will contribute to saving European citizens’ lives and help ensuring an optimal quality of life to disease survivors. To reach a new level of understanding, UNCAN.eu will take advantage of recent advances in research data generation and data sciences. Reliable, high-quality cancer research data generated by experimental model analysis and collected from longitudinal follow-up of cancer patients will be shared and integrated at an unprecedented scale within a Federated Cancer Research data hub, in the context of the General Data Protection Regulation. This information will be used by relevant players in Europe and beyond to address urgent and essential scientific and medical challenges in cancer prevention, early diagnosis, treatment and survivorship, in males and females of various ages. These challenges, identified in close interaction with European patients and citizens, will be tackled through competitive, ambitious and innovative, cross-border and trans-disciplinary research programmes built in a problem-solving manner. The definition of challenges will integrate inequalities in cancer research across regions and member states in order to boost the research potential of less-developed regions in Europe. Players will be committed to open science principles, including FAIR (findable, accessible, interoperable, and reusable) guiding principles for scientific data collection, management and stewardship. The new understanding gained from the collection and analysis of this wealth of data will apply secondarily to other diseases.