The chapter examines the current problem associated with the application of mathematical methods, in particular the evolutionary-simulation model (ESM), in simulating the processes of the patient's treatment plan in order to prove the correctness of the decision made. From the perspective of the system approach the technology of ESM description is considered, the main stages of the development of simulation models for determining medical parameters and the decision-making process in the implementation of the treatment plan are outlined. There are examples of sufficiently detailed description of four decision-making tasks in biophysical and biomedical research using ESM: mutually compensating biophysical processes and biophysical processes, planning of experiments and processing of their results, medical and biological norms. A new approach to the implementation of the multi-agent principle based on the theory of equilibrium random processes in the field of immunology is proposed. The analysis of the model of immune process proposed by G. I. Marchuk revealed that this model does not allow to take into account the high uncertainty of running processes, their random nature, external factors and discreteness. These problems can be eliminated if the immune process is represented as the ESM. An ESM of the immune process, based on which an intelligent service for simulating and prognosticating the organism's immune response can be developed, is proposed. Prospects of the ESM development for solving other applied problems in medicine are formulated.