With the promotion of an ecological civilization philosophy and a sustainable development strategy, solid waste classification and collection has become an emerging issue in China. Based on the three dimensions of sustainable development, namely economy, society, and environment, the route optimization model of waste collection and transportation is constructed. In order to solve the model aiming to maximize the benefits of sanitation companies under the constraints of workload balance, transportation cleanliness, and route changes due to cost factors, we combine the non-dominated sorting genetic algorithm III with simulated annealing. According to the characteristics of the problem, the probabilistic insertion method is incorporated to generate the initial solution, and the adaptive mutation operator is added to improve the population diversity. Finally, a real case in Xuhui District, Shanghai, a megacity taking the lead in 2019 in mandating a separated collection policy, is presented to verify the proposed model’s performance. The results provide a decision solution for dispatching the collection route of vehicles with some references for sanitary companies.