<jats:title>Abstract</jats:title><jats:p>Predicting anthropogenic impacts on benthic marine ecosystems is of great importance for conservation. Climate change models have indicated that increasing seawater temperatures will drive shifts in the distribution of benthic organisms due to species‐specific thermal tolerances. When combined with other stressors such as pollutants, interactive effects may lead to even greater impacts. Microplastics (MP), as a marine pollutant, have been shown to elicit responses in organisms but often at concentrations far greater than experienced in the environment and with short‐term exposure times. Assessing long‐term interactive effects of MP pollution and ocean warming on benthic marine organisms has not been previously addressed. A unique mesocosm facility was constructed on the island of Helgoland, in the southern North Sea, to explore the combined impacts of these two factors. The multi‐factorial experimental system is composed of 16 independent benthic mesocosms, utilizing novel features and methods for the continuous generation of climate change and MP exposure scenarios, while retaining natural conditions for other environmental parameters. We provide a description of the system design and methods, followed by an operational performance assessment during a 10‐month exposure experiment with European flat oysters (<jats:italic>Ostrea edulis</jats:italic>), evaluated on the accuracy of exposure scenario control and the degree of realism achieved. We demonstrate the novel application of kinetic modeling for generating environmentally relevant MP exposure conditions (+ 25 MP L<jats:sup>−1</jats:sup>), and highlight the mesocosm systems suitability for studying chronic effects of MP pollution and ocean warming on benthic marine ecosystems through its real‐world application.</jats:p>