Isothermal titration calorimetry (ITC) was introduced as a highly sensitive tool to analyze interactions in polymer and material science by their thermodynamic patterns. The thermodynamic parameters Delta H, Delta S, Delta G, K-B, and the stoichiometric ratio of the interactions in a complex organic-inorganic hybrid system were determined in a single experiment. In particular, the adsorption behavior of surface-active amphiphilic copolymers, bearing different types of anchor groups (nonionic, zwitterionic, and acidic), with SiO2 nanoparticles in a multicomponent solvent system was investigated. The knowledge of the thermodynamic parameters of the interaction provided, beside its strength, a detailed understanding of its mechanism. Particularly, for the production of the nanocomposites, this knowledge might lead to a more rational and optimized design of these materials.