The possible origins and the magnitude of an electric current arising in nanofilm metal–semiconductor heterostructures when the metal surface is used to catalyze an exothermic chemical reaction are discussed. Two key mechanisms are considered that are responsible for the current generation: electron motion due to a temperature drop across the metal–semiconductor interface (thermionic emission mechanism) and the Seebeck effect in the two layers (thermoelectric mechanism). It is predicted that (i) current up to 10−3 A·cm−2 can arise, (ii) thermoelectric mechanism due to the Seebeck effect in the semiconductor layer plays a dominant role for the current generated under stationary chemical reaction conditions, and (iii) thermoelectric current strongly depends on the temperature. The carrier transport through the metal–semiconductor interface is described by the thermionic emission theory. The obtained results are discussed in view of the experimental data reported earlier for the chemical reaction-induced currents in metal/n-Si structures.