Recently, issues of climate change, environment abnormality, individual requirements, and national defense have caused extensive attention to the commercial, scientific, and military development of unmanned surface vehicles (USVs). In order to design high-quality routes for a multi-sensor integrated USV, this work improves the conventional particle swarm optimization algorithm by introducing the greedy mechanism and the 2-opt operation, based on a combination strategy. First, a greedy black box is established for particle initialization, overcoming the randomness of the conventional method and excluding a great number of infeasible solutions. Then the greedy selection strategy and 2-opt operation are adopted together for local searches, to maintain population diversity and eliminate path crossovers. In addition, Monte-Carlo simulations of eight instances are conducted to compare the improved algorithm with other existing algorithms. The computation results indicate that the improved algorithm has the superior performance, with the shortest route and satisfactory robustness, although a fraction of computing efficiency becomes sacrificed. Moreover, the effectiveness and reliability of the improved method is also verified by its multi-sensor-based application to a USV model in real marine environments.