Global biodiversity is declining at an unprecedented rate in response to multiple environmental stressors. Effective biodiversity management requires deeper understanding of the relevant mechanisms behind such ecological impacts. A key challenge is understanding synergistic interactions between multiple stressors and predicting their combined effects. Here we used Daphnia magna to investigate the interaction between a pyrethroid insecticide esfenvalerate and two non-chemical environmental stressors: elevated temperature and food limitation. We hypothesized that the stressors with different modes of action can act synergistically. Our findings showed additive effects of food limitation and elevated temperature (25 °C, null model effect addition (EA)) with model deviation ratio (MDR) ranging from 0.7 to 0.9. In contrast, we observed strong synergistic interactions between esfenvalerate and food limitation at 20 °C, considerably further amplified at 25 °C. Additionally, for all stress combinations, the synergism intensified over time indicating the latent effects of the pesticide. Consequently, multiple stress substantially reduced the lethal concentration of esfenvalerate by a factor of 19 for the LC50 (0.45–0.024 μg/L) and 130 for the LC10 (0.096–0.00074 μg/L). The stress addition model (SAM) predicted increasing synergistic interactions among stressors with increasing total stress.