Climate change is already impacting marine ecosystems across a range of scales, from individual physiology, to changes in species interactions and community structure, and ultimately to patterns in geographic distribution. Predicting how marine ecosystems will respond to environmental change is a significant challenge because vulnerability to climatic and non-climatic stressors is highly variable, and depends on an organism's functional traits, tolerance to stressors, and the environment in which it lives. We present a mechanistic approach based on biophysical and dynamic energy budget models that integrates the cumulative effects of multiple environmental stressors (temperature and food) and stress associated with the presence of predators (the “fear of being eaten”), with the functional traits of an organism. We describe how multiple factors such as feeding time, food availability, and weather can be combined into a few simple metrics and explore how the physiological and behavioral impacts of predation risk can be included in this framework by altering prey feeding time and performance. Importantly, we highlight several critical gaps in our basic understanding of the fundamental mechanisms that drive responses to multiple stressors in natural systems. The framework presented here is, thus, intended to serve as a guide for the formulation of explicit, testable hypotheses and further controlled experimentation.