Anthropogenic activities increase pesticide contamination and biological invasions in freshwater ecosystems. Understanding their combined effects on community structure and on ecosystem functioning presents challenges for an improved ecological risk assessment. This study focuses on an artificial stream mesocosms experiment testing for direct and indirect effects of insecticide (chlorantraniliprole - CAP) exposure on the structure of a benthic macroinvertebrate freshwater community and on ecosystem functioning (leaf decomposition, primary production). To understand how predator identity and resource quality alter the community responses to chemical stress, the mediating effects of an invasive predator species (crayfish Procambarus clarkii) and detritus quality (tested by using leaves of the invasive Eucalyptus globulus) on insecticide toxicity were also investigated. Low concentrations of CAP reduced the abundance of shredders and grazers, decreasing leaf decomposition and increasing primary production. Replacement of autochthonous predators and leaf litter by invasive species decreased macroinvertebrate survival, reduced leaf decomposition, and enhanced primary production. Structural equation modeling (SEM) highlighted that CAP toxicity to macroinvertebrates was mediated by the presence of crayfish or eucalypt leaf litter which are now common in many Mediterranean freshwaters. In summary, our results demonstrate that the presence of these two invasive species alters the effects of insecticide exposure on benthic freshwater communities. The approach used here also allowed for a mechanistic evaluation of indirect effects of these stressors and of their interaction on ecosystem functional endpoint, emphasizing the value of incorporating biotic stressors in ecotoxicological experiments.