The chapter deals with the road transport optimization and estimation of reduced CO2 emissions. To reduce the latter, several approaches were adopted, like alternative technologies, sustainable community changes, and changes in driving behavior. Another possible approach is to reduce the vehicle miles of traveled (VMT) by the means of transport optimization. In this chapter, the heuristic optimization approach for VMT reduction is firstly presented and tested for the case of School Bus Routing Problem. Afterwards, main focus is dedicated to the models for estimation of reduced CO2 emissions. Herein, MEET emission model is integrated into the Monte Carlo based scenario playing algorithm, which calculates the total CO2 emissions in the dependence of the randomly independently changing average speeds of the vehicles of the driving fleet. This algorithm is applied to the optimized situation, and the calculated results are compared with the unoptimized case. Results show that the applied optimization concept can significantly reduce the CO2 emissions compared to unoptimized conditions.