In this paper, a hierarchical optimization procedure for reaction path synthesis is presented in which the overall reaction is not necessarily desirable with respect to the thermodynamics or mechanism of reaction. According to the specified raw materials, desired product, and probable byproducts, the overall reactions are determined through the generation method of simple stoichiometric reactions and evaluated by economic potential and other criteria; such as thermodynamic feasibility and kinetic desirability. For an overall reaction that is unachievable thermodynamically or kinetically while potentially desirable with respect to profit, a novel procedure for overall reaction decomposition by adding intermediate chemicals is proposed to realize it by several thermodynamically feasible division reactions. When this method is used, the optimal solution of reaction path synthesis can be either an overall reaction or several division reactions. A case study is described to illustrate the proposed procedure.