Microplastics are a diverse contaminant with complex physical and chemical properties. While microplastics have varying effects, most studies to date have focused on evaluating microplastics as a single stressor under stable environmental conditions. In reality, organisms are exposed to more than microplastics, and thus, it will be increasingly important to evaluate the effects of microplastics in the context of multiple anthropogenic stressors. Here, we highlight the need to assess the physical and chemical effects of microplastics, as well as their interactions with other anthropogenic stressors, at multiple levels of biological organization (i.e., sub-organismal, individual, population, community, ecosystem). We also outline research priorities and recommendations that will facilitate ecotoxicological assessments to better encompass the multidimensionality of microplastics as environmental conditions continue to change. By taking a multi-stressor ecotoxicological approach, we can work toward a better understanding of microplastic and other stressor effects at multiple levels of biological organization to help inform robust, evidenced-based policy and management decisions.