Herein reported is the highly selective [2 + 2] cross-photodimerization of olefins within a self-assembled coordination cage that acts as a molecular flask in an aqueous medium. An M(6)L(4) coordination nanocage that self-assembles from six Pd(II) complexes and four tridentate ligands accommodates two different kinds of large olefin molecules such as acenaphthylene and 5-ethoxynaphthoquinone in a pairwise selective fashion. This prerequisite recognition mode makes possible the selective [2 + 2] cross-photodimerization of the olefins within the cavity. The reaction is extremely efficient in terms of reaction rate, stereoselectivity, and, most importantly, pairwise selectivity. Maleimide derivatives, which themselves are photochemically inactive under ordinary conditions, are also cross-dimerized with acenaphthylene or dibenzosuberenon quite efficiently. These results are in sharp contrast to those of common photodimerization in organic media, where the yields and selectivities are generally poor to moderate. The key step of the exclusive formation of the cross-dimers stems from the selective formation of ternary complexes before irradiation, which is governed by the size compatibility of the guests with the confined space of the cavity.