We describe the AMBITION project, a mission to return the first-ever cryogenically-stored sample of a cometary nucleus, that has been proposed for the ESA Science Programme Voyage 2050. Comets are the leftover building blocks of giant planet cores and other planetary bodies, and fingerprints of Solar System’s formation processes. We summarise some of the most important questions still open in cometary science and Solar System formation after the successful Rosetta mission. We show that many of these scientific questions require sample analysis using techniques that are only possible in laboratories on Earth. We summarize measurements, instrumentation and mission scenarios that can address these questions. We emphasize the need for returning a sample collected at depth or, still more challenging, at cryogenic temperatures while preserving the stratigraphy of the comet nucleus surface layers. We provide requirements for the next generation of landers, for cryogenic sample acquisition and storage during the return to Earth. Rendezvous missions to the main belt comets and Centaurs, expanding our knowledge by exploring new classes of comets, are also discussed. The AMBITION project is discussed in the international context of comet and asteroid space exploration.