Heterogeneous catalysis is a critical component in the improvement of existing technologies and development of new solutions in the area of clean energy and sustainability. Combining vibrational spectroscopies with quantum chemical calculations can provide molecular-level information on the structure of catalytic surfaces and reaction pathways. As an initial step, comparison between experimental and computational vibrational spectra can be used for identification of adsorption modes for reactants and products and also for determination of the nature of stable surface species under reaction conditions. In subsequent steps, quantum chemical models calibrated based on stable reaction species on appropriately selected surfaces can be used for evaluation of multiple reaction pathways, identification of transient reaction intermediates, and development of reaction mechanisms for incorporation into kinetic models and description of observable reaction rates. This methodology is illustrated with two spectroscopic techniques: infrared and high resolution electron energy loss spectroscopies and two catalytic systems: Fischer-Tropsch synthesis over Co/TiO2 catalysts and hydrocarbon reactivity on catalytic Pt-Sn alloys.