This white paper proposes that AMBITION, a Comet Nucleus Sample Return mission, be a cornerstone of ESAs Voyage 2050 programme. We summarise some of the most important questions still open in cometary science after the successes of the Rosetta mission, many of which require sample analysis using techniques that are only possible in laboratories on Earth. We then summarise measurements, instrumentation and mission scenarios that can address these questions, with a recommendation that ESA select an ambitious cryogenic sample return mission. Rendezvous missions to Main Belt comets and Centaurs are compelling cases for M-class missions, expanding our knowledge by exploring new classes of comets. AMBITION would engage a wide community, drawing expertise from a vast range of disciplines within planetary science and astrophysics. With AMBITION, Europe will continue its leadership in the exploration of the most primitive Solar System bodies.