Owing to the often-similar physical and chemical properties of structural isomers of organic molecules, large efforts have been made to develop efficient strategies to isolate specific isomers. However, facile separation of regioisomeric compounds remains difficult. Here we demonstrate a universal organometallic capsule in which two silver centers are rigidly separated from each other by two tetranuclear [Rh4] pyramidal frustums, which selectively encapsulate a specific isomer from mixtures. Not only is the present heterometallic capsule suitable as a host for the encapsulation of a series of aromatic compounds, but also the receptor shows widely differing specificity for the various isomers. Direct experimental evidence is provided for the selective encapsulation of a series of para (p)-disubstituted benzene derivatives, such as p-xylene, p-dichlorobenzene, p-dibromobenzene, and p-diiodobenzene. The size and shape matching, as well as the Ag-π interactions, are the main forces governing the extent of molecular recognition. The encapsulated guest p-xylene can be released by using the solid-liquid solvent washing strategy, and the other guest molecules are easily liberated by using light stimulus.