The vehicle routing and scheduling (VRS) problem with multi-objective and multi-constraint is analyzed, considering the complexity of the modern logistics in city economy and daily life based on the system engineering. The objective and constraint includes loading, the dispatch and arrival time, transportation conditions,total cost,etc. An information model and a mathematical model are built,and a method based on knowledge and biologic immunity is put forward for optimizing and evaluating the programs dimensions in vehicle routing and scheduling with multi-objective and multi-constraints. The proposed model and method are illustrated in a case study concerning a transport network, and the result shows that more optimization solutions can be easily obtained and the method is efficient and feasible. Comparing with the standard GA and the standard GA without time constraint,the computational time of the algorithm is less in this paper. And the probability of gaining optimal solution is bigger and the result is better under the condition of multi-constraint.