Understanding the cumulative effects of multiple stressors is a research priority in environmental science. Ecological models are a key component of tackling this challenge because they can simulate interactions between the components of an ecosystem. Here, we ask, how has the popular modeling platform Ecopath with Ecosim – well-known for applications in fisheries – been used to model human impacts related to climate change, land and sea use, pollution, and invasive species? We conducted an exhaustive, systematic literature review encompassing 163 studies covering mostly aquatic ecosystems. The most modeled stressors were climate change (59 studies), habitat loss (21), species introductions (21), and eutrophication (19), using a range of modeling techniques. Despite this apparently comprehensive coverage, we identify four substantial gaps. First, only 13% of studies investigated three or more stressors, with most studies focusing on single stressors. Compounding this incomplete view, many studies modeled only one of many pathways through which each stressor is known to affect ecosystems. Second, various methods have been applied to define environmental response functions representing the effects of single stressors on species groups. These functions can have a large effect on the timing and magnitude of ecological changes, but best practices for deriving them are yet to emerge. Third, human dimensions of environmental change – except for fisheries – were rarely considered. For example, only 3% of studies reported indicators representing non-extractive ecosystem services. Fourth, only 3% of studies used statistical research designs that allow attribution of ecosystem changes to stressors’ direct effects and interactions, such as factorial (computational) experiments. None made full use of the statistical possibilities that arise when simulations can be repeated 1,000s of times with controlled changes to the inputs. We argue that all four gaps are feasibly filled by integrating ecological modeling with advances in other subfields of environmental science and in computational statistics.