In this paper, the perturbed matrix method (PMM) is used in combination with basic statistical mechanics, to develop a general theoretical method to model chemical reactions and related molecular processes in complex systems, i.e., liquids, biochemical systems, macromolecules, etc. The main feature of this approach consists of the explicit treatment of the coupling between the reaction center and the fluctuating atomic-molecular environment, providing a rigorous statistical mechanical description of the chemical event. A special attention is dedicated to the approximations and assumptions necessary to use such a theoretical procedure in combination with simulation data.