In terms of ligand-directed synthetic strategy, multifunctional metal−organic frameworks (MOFs) could be assembled by employing organic ligands with nitrogen-containing heterocycles, which could serve as Lewis base sites in crystallized porous frameworks. Here, the acidic one-pot hydrothermal reaction of CaCl 2 , Zn(NO 3 ) 2 , and 2,4,6-tri(2,4-dicarboxyphenyl)pyridine (H 6 TDP) generates one robust honeycomb-shaped double-walled), which has the excellent physicochemical characteristics of nanoscopic channels, high porosity (58.3%), large specific surface area, and high heat/water-resisting property. To the best of our knowledge, this is the first 3s−3d dinuclear [CaZn(CO 2 ) 6 (OH 2 )]based nanoporous host framework, whose activated state possesses the coexistence of Lewis acid−base sites including four-coordinated Zn 2+ ions, four-coordinated Ca 2+ ions, uncoordinated carboxyl oxygen atoms, and N pyridine atoms. As expected, because of the coexistence of Lewis acid−base nature, desolvated NUC-21 displays satisfactory catalytic activity on the chemical cycloaddition of various epoxides with CO 2 into the corresponding alkyl carbonates under comparatively mild conditions. Furthermore, the efficient conversion of benzaldehydes and malononitrile confirms that NUC-21 is simultaneously a bifunctional heterogeneous catalyst for Knoevenagel condensation reactions. Hence, the achievements broaden the way for assembling nanoporous multifunctional MOFs by employing ligand-directed synthetic strategy, which can accelerate the transformation from simple structural research to socially demanding applications.