Shallow aquatic systems are abundant in agricultural landscapes but highly susceptible to suffer from climate warming and agricultural run-off (ARO). Regime shifts between the dominance of microalgae or macrophytes may occur depending on the level and interaction of multiple stressors acting on the system. The main objectives of our French-German project CLIMSHIFT were (I) to understand the response of shallow aquatic ecosystems to warming and ARO based on a mechanistic understanding of stressor interactions and community responses; (II) to evaluate if the stressors act in an additive, synergistic or antagonistic way on organism physiology, community and ecosystem processes; and (III) to determine potential thresholds for shifts in ecosystem functions for single and combined stressors. CLIMSHIFT included a series of indoor microcosm experiments testing different exposure scenarios to ARO combined with warming on a benthic-pelagic community typical for shallow aquatic systems. Those were upscaled to larger outdoor mesocosms using natural plankton and periphyton communities. In all micro- or mesocosm experiments, we observed regime shifts from the good ecological status with a dominance by macrophytes to a degraded status with a dominance by either phytoplankton, periphyton or blanketing algae. Our CLIMSHIFT project proved that a well-planned experimental design based on a combination of micro- and mesocosm experiments allows to study complex multiple stressor effects on shallow aquatic systems, and to disentangle direct and indirect effects as well as stressor-interaction patterns. Combined nutrient (nitrate) and pesticide effects led to a range of direct and indirect effects on primary producers and consumers, with the most visible being the shift from macrophyte dominance to the dominance either phytoplankton, periphyton or blanketing filamentous algae. Nitrate and warming acted synergistically with pesticides, leading to stronger macrophyte decline. Further, warming can lower the threshold for such shifts. Effects of agricultural run-off on these systems are especially severe in spring, when average rainfall is high and submerged macrophytes start to grow. Lowering local stressors can help maintain shallow aquatic systems in a good ecological status even when global stressors such as climate warming prevail.