Construction of supramolecular structures with internal functionalities is a promising approach to build enzyme‐like cavities. The endo‐functionalized Pd12L24 and Pd2L4 coordination cages represent the most successful systems in this regard. However, these systems mainly contain one type of endo‐moiety. We herein provide a solution for the controlled endo‐functionalization of Pd2L4 cages. Site‐selective introduction of the endo‐functional group was achieved through the formation of heteroleptic Pd2(LA)2(LB)(LC) cages. Using two orthogonal steric control elements is the key for the selective formation of the hetero‐assemblies. We demonstrated the construction of two hetero‐cages with a single internal functional group as well as a hetero‐cage with two distinct endohedral functionalities. The endo‐functionalized hetero‐cages bound sulfonate guests with fast‐exchange dynamics. This strategy provides a new solution for the controlled endo‐functionalization of supramolecular cavities. Unprecedented heteroleptic Pd2 (LA)2 (LB) (LC) supramolecular cages were selectively constructed by taking advantage of a pair of orthogonal steric control elements encoded in distinct ligands. This strategy allows the site‐selective introduction of distinct endo‐functionalities into the cavity of the heteroleptic cage.