Controlling cyanobacterial blooms is not only an engineering and technical issue but also an optimization problem in environment management. Under budget constraints, a novel simulation-based optimization model for cyanobacterial control is constructed in this study. The simulation model is used for simulating cyanobacteria growth and diffusion processes. The optimization model is utilized to determine the optimal search and treatment path. Through the interactive coupling of simulation modeling and resource allocation optimization, this research provides decision-makers with new operational guidelines for cyanobacterial control. Our test results demonstrate that the initial invasion frequency has a greater economic impact than invasion abundance. The nearby cells to the initial invasion are affected first, and then the influence radiates outward in a diffusion pattern. Using a slow search speed and a treatment frequency of every 10 days can achieve the lowest possible economic losses in most test scenarios. Moreover, we also find that the optimal search and treatment paths revolve around the initial invasion location. This study is a typical interdisciplinary research, which can assist water resource managers in making more accurate decisions regarding cyanobacteria removal paths, removal frequencies, and treatment speeds.