Atomistic understanding of complex surface phenomena such as heterogeneous catalysis or storage and separation of energy-relevant gases in nanoporous materials (zeolites; metal-organic frameworks, MOFs) requires knowledge about reaction energies and energy barriers for elementary steps. This is difficult to obtain from experiment since the number of possible chemical, adsorption/desorption, and diffusion steps coupled to complex reaction networks is large, and so is the number of possible surface sites. Here is an important role of quantum chemistry which can provide rate and equilibrium constants for elementary steps "ab initio." To be useful, the predictions have to reach chemical accuracy (4 kJ/mol) which is difficult to achieve because realistic models of the surface systems may comprise of the order of a thousand atoms. While density functional theory (DFT) as a rule cannot be trusted to yield results within chemical accuracy limits, methods that are accurate enough (Coupled Cluster with Single, Double, and perturbative Triple Substitution, CCSD(T)) cannot be applied because of their exponential scaling with system size. This Account presents a hybrid high-level-low-level quantum method that combines DFT with dispersion for the full periodic system with second order Møller-Plesset perturbation theory (MP2) for the reaction site within a mechanical embedding scheme. In addition, to check if MP2 is accurate enough, we calculate Coupled Cluster (CC) corrections with Single, Double, and perturbatively treated Triple substitutions (CCSD(T)) for sufficiently small models of the reaction site. This multilevel hybrid MP2:DFT-D+ΔCC method is shown to yield chemical accuracy for a set of 12 molecule-surface interaction systems for which reliable experimental data are available. For CO/MgO(001), the history of the experiment-theory comparison illustrates two problems: (i) Do experiment and theory look at the same surface site? (ii) Does theory calculate the same quantity as derived from experiment? The hybrid MP2:DFT-D+ΔCC data set generated includes the MgO(001) surface, the Mg2(dobdc) metal-organic framework, and the proton forms of the CHA and MFI zeolites interacting with the H2, N2, CO, CO2, CH4, and C2H6 molecules. It serves two purposes. First, it will be useful for testing density functionals with respect to their performance for molecule-surface interactions. Second, it establishes the hybrid MP2:DFT-D+ΔCC method as a reliable and powerful tool for ab initio predictions of adsorption and reaction energies as well as energy barriers when testing reaction mechanisms. For adsorption of small molecules in MOFs, isotherm predictions have reached a level of accuracy that deviations between theoretical predictions and experiments indicate sample imperfections. For elementary steps of the industrially important methanol-to-olefin process, our hybrid MP2:PBE+D+ΔCC calculations yield rate constants in agreement with experiment within chemical accuracy limits, finally achieving for molecule-surface reactions which was possible so hitherto only for gas phase reactions involving not more than 10 atoms.