Crown-of-thorns starfish (CoTS) are major coral predators on the Great Barrier Reef (GBR) and are managed through manual control (culling). Knowledge gaps encompass manual control efficacy, interactions with perturbations, and how to best deploy efforts to improve coral outcomes given local conditions. Using Models-of-Intermediate-Complexity-for-Ecosystem-assessment (MICE), we examined manual control efficacy under bleaching, cyclone, and CoTS outbreak conditions. We found control could improve coral cover up to 14% and shorten outbreak duration by 2-4 years. Our results supported the notion we defined as Effort Sinks, whereby culling CoTS to very low levels had poorer outcomes across all sites due to resource constraints and diminishing returns. Simulations showed culling was most effective where corals were less susceptible to thermal stress, experienced lower accumulated thermal stress, and under reduced CoTS recruitment. These varied among and within reefs. Current culling thresholds (ecological targets) appear robust to variation in coral growth rates, and region-specific thresholds based on coral growth rates may not be needed to limit coral loss across the GBR. Our recent MICE applications are helping to inform coral-CoTS based control targets and underscore the importance of managing pest species interactions alongside assets rather than purely focusing on the pest species.