Shallow lakes provide essential ecological and environmental services but are exposed to multiple stressors, including agricultural runoff (ARO) and climate warming, which may act on different target receptors disrupting their normal functioning. We performed a microcosm experiment to determine the individual and combined effects of three stressors—pesticides, nitrate and climate warming—on two trophic levels representative of communities found in shallow lakes. We used three submerged macrophyte species (Myriophyllum spicatum, Potamogeton perfoliatus, Elodea nuttallii), eight benthic or pelagic microalgal species and three primary consumer species (Daphnia magna, Lymnaea stagnalis, Dreissena polymorpha) with different feeding preferences for benthic and pelagic primary producers. Eight different treatments consisted of a control, only nitrate, a pesticide cocktail, and a combination of nitrate and pesticides representing ARO, each replicated at ambient temperature and +3.5°C, mimicking climate warming. Pesticides negatively affected all functional groups except phytoplankton, which increased. Warming and nitrate modified these effects. Strong but opposite pesticide and warming effects on Myriophyllum drove the response of the total macrophyte biomass. Nitrate significantly suppressed Myriophyllum final biomass, but not overall macrophyte and microalgal biomass. Nitrate and pesticides in combination caused a macrophyte decline, and the system tipped towards phytoplankton dominance. Strong synergistic or even reversed stressor interaction effects were observed for macrophytes or periphyton. We emphasize the need for more complex community- and ecosystem-level studies incorporating multiple stressor scenarios to define safe operating spaces.