Abstract: Solar system boundary exploration will enhance our understanding of the formation and evolution of the Solar system, which is an important issue of future deep space exploration. As the boundary is far from Earth, the energy needed in the exploration is huge. Thus, gravity-assist technique is essential to carry out Solar system boundary exploration mission. This paper aims at multiple gravity-assist transfer design in Solar system boundary exploration missions. First, processing method of goals and constraints in Solar system boundary exploration are studied. And a progressive nested-loop optimization method combining two different kinds of multiple gravity-assist dynamics is provide, as well as the detailed steps. At last, taking the nose and the tail of Solar system boundary for example, the optimal fly-by sequences are provided, proofing the validity of the method. The simulations demonstrates that the optimal multiple gravity –assists trajectories is Earth-Venus-Earth-Earth-Jupiter-Saturn- nose of Solar system, and the optimal multiple gravity –assists trajectories is Earth-Venus-Earth-Earth-Neptune-tail of Solar system. The research will provide the reference for the target selection and mission planning for future Solar system exploration in China.