Artificial molecular architecture from a large number of subcomponents (>50) via self-assembly remains a formidable challenge for chemists. Reaction of 38 components [14 Ni2+ and 24 N-methyl-1-(4-imidazolypmethanimine] under solvothermal conditions reproducibly leads to the formation of a high-symmetry coordination cage. This polyhedral cage can also be obtained in high yield by self-assembly of 62 commercially available subcomponents (24 methylamine, 24 4-formylimidazole, and 14 Ni2+) under mild conditions involving synchronized formation of both dynamic covalent bonds and coordination bonds. Guest molecules (e.g., water, methylamine, and methanol) are randomly imprisoned in the cage.