Multidentate materials formed by simply mixing heterogeneous and homogeneous components are promising for construction of versatile active sites on the surface of heterogeneous compounds, however, to the best of our knowledge, there are no reports on such materials. Self-assembly of hetero-hybrid catalytic materials occurs when heterogeneous catalysts having adjacent Lewis acid-Lewis base sites are mixed with an organic modifier that contains at least two Lewis base functional groups. Here we demonstrate the strategy by combining cerium oxide and 2-cyanopyridine that self-assembles to form a charge-transfer complex in methanol that exhibits a 2,000-fold increase in reaction rate for hydromethoxylation of acrylonitrile with high selectivity compared with cerium oxide or 2-cyanopyridine alone. The catalytic system is applied to the transesterification and Knoevenagel condensation affording 14-fold and 11-fold higher activity, respectively, than cerium oxide alone. These results demonstrate the potential versatility of the catalytic system and the generality of the catalyst preparation strategy.