In the context of global change, marine organisms are subjected not only to gradual changes in abiotic parameters, but also to an increasing number of extreme events, such as heatwaves. However, we still know little about the influence of heatwaves on the structure of marine communities, and experimental studies are needed to test the impact of heatwaves alone and in combination with other environmental drivers. Here, we conducted a mesocosm experiment to assess the potential impact of heatwaves on plankton communities, which we did under ambient and future environmental conditions. To simulate future environmental conditions, we simultaneously manipulated temperature and pH based on IPCC predictions for 2100, and dissolved N : P ratios based on the conditions expected in European coastal zones. While we did not observe any effects of simulated heatwaves on phytoplankton abundances, we identified that future environmental conditions may favor smaller phytoplankton species and that additional heatwaves may especially favor small phytoflagellates and coccolithophores. We also observed that future environmental conditions may reduce the abundances and modify the species composition of bacterioplankton, microzooplankton, and mesozooplankton, and that heatwaves may exacerbate these effects. Using a unique approach to examine the potential impacts of heatwaves under current and future environmental conditions on a natural multi-trophic marine plankton community, we show that the combination of multiple global change drivers has the potential to perturb the entire basis of marine food webs.