Multivalent cooperativity plays an important role in the supramolecular self-assembly process. Herein, we report a remarkable cooperative enhancement of both structural integrity and metal ion selectivity on metal-organic M L tetrahedral cages self-assembled from a tris-tridentate ligand (L ) with a variety of metal ions spanning across the periodic table, including alkaline earth (Ca ), transition (Cd ), and all the lanthanide (Ln ) metal ions. All these M L cages are stable to excess metal ions and ligands, which is in sharp contrast with the tridentate (L ) ligand and bis-tridentate (L ) ligand bearing the same coordination motif as L . Moreover, high-precision metal ion self-sorting is observed during the mixed-metal self-assembly of tetrahedral M L cages, but not on the M L counterparts. Based on the strong cooperative metal ion self-recognition behavior of M L cages, a supramolecular approach to lanthanide separation is demonstrated, offering a new design principle of next-generation extractants for highly efficient lanthanide separation.