Abstract：Based on the conception of simple stoichiometric reaction, a two-tier optimization method for complex reaction path synthesis problems is addressed. On the first level, a feasible and economic optimal overall reaction is searched by enumerating all simple stoichiometric reactions. Then, these reactions are sorted by gross profits. And evaluations for each reaction from kinetic, thermodynamic and environmental aspects are made. The feasible reaction that has the best profit will be appointed as the reference reaction. The overall reaction of which the profit is less than that of the reference reaction will be abnegated. Those reactions that have better economic potential but are unfeasible will then be tried to be decomposed into several feasible division reactions that take place under different operating conditions on the second level. If the decomposition is possible, the result will be the best reaction path; otherwise the reference reaction is the best result. A case study shows that the method can efficiently solve practical reaction path synthesis problems.