The development of new nanomaterials has been among the most important research areas in nanoscience and nanotechnology for possible applications in catalysis, drug delivery, nanoelectronics and sensors. Numerous efforts have concentrated on the synthesis of multifunctional nanomaterials, which contain two or more functional groups. These include bifunctional mesoporous materials that could have highly efficient catalytic activity by the cooperative action of the two or more functional groups or catalytic sites in the materials. Herein, novel solvent-assisted synthetic methodologies for various efficient and selective bifunctional acid-base catalysts have been established. By using simple solvent assisted post-grafting method, it has been possible to spatially-isolate organoamines onto mesoporous materials, improving their catalytic activities. Some of the materials obtained have also been among the most efficient bifunctional acid-base catalysts ever reported with typical yields of ∼100% in 15 min for the Henry (nitroaldol condensation) reaction. Furthermore, further investigation enabled the determination of generic and strong correlations between the solvent properties (polarity and dielectric constant) and surface density of grafted groups on organic functionalized mesoporous materials. Specifically, it is found that the polarity and dielectric constants of solvents used for grafting organosilanes on mesoporous materials strongly affect the surface density of many types of grafted organic groups, the degree of their site-isolation, and the catalytic properties of the resulting materials. Polar, protic solvents give less dense and more site-isolated organoamine (or catalytic sites) but more efficient multifunctional nanoporous catalysts. However, dipolar, protic and non-polar solvents give from small to large density of organoamine groups and from poor-to-high catalytic efficiencies. The effect of the surface density and the spacing between grafted organoamines (and residual ungrafted silanols) of organic functionalized mesoporous materials on their (cooperative) catalytic activity for the Henry reaction is also described. The catalytic properties of these organoamine functionalized mesoporous materials are found to depend on the size and flexibility of the organoamines, as studied using both shorter and longer monoamine, diamine and triamine functionalized samples. Samples grafted with monoamine groups in ethanol and with diamine and triamine in toluene for 5 h give ∼100% yield within 16 min for the Henry reaction. However, the corresponding monoamine-grafted sample in toluene and the diamine- and triamine-grafted samples in ethanol result in the ∼100% yield after 1 h. The samples with an optimum concentration of grafted organoamines, dubbed as Critical Density of Organic Grafted Groups (CDOGG), and the samples with the most favorable site-isolated amine groups or most favorable amine-silanols cooperative catalytic activity gives the highest possible catalytic efficiency for Henry reaction. Moreover the degree of site-isolation of the amine groups, which affect the material’s catalytic properties, is also elucidated by a new calorimetric method developed in this work. Finally, a synthetic method to obtain highly efficient and selective mesoporous catalyst containing secondary and tertiary amine groups is discussed. The material’s ability to selectively give either β-nitrostyrene or nitroalcohol products from the Henry reaction is demonstrated. Results of these studies can be extended for the rational design and synthesis of a wide range of efficient multifunctional catalysts for a number of other reactions.