Widespread tree mortality in response to drought, increasing temperatures, and insects/pathogens is not only altering forests globally, but is expected to increase in distribution and frequency as climate change progresses. Widespread tree mortality is having – and will continue to have – massive ecological effects on community composition, wildlife, water resources, and the global carbon cycle. Two important lines of research have emerged to tackle this problem, one aimed at understanding the physiological mechanisms of tree mortality, and another focused on tree-killing insects and pathogens. The attention in these two fields is warranted, but even more progress can be made with an integrative approach that links these lines of research. Understanding abiotic physiological influences on tree resource allocation strategies, mechanisms constraining investment in effective chemical defenses against insects and pathogens, and the genetic underpinnings mediating these responses is now necessary to make significant advances in tree mortality research. Our ability to accurately predict when and where trees will die in response to climate stress is poor due to our inability to incorporate first principles of ecophysiology, secondary metabolism and insect responses. Specifically, our lack of knowledge with regards to processes that initiate major biotic disturbances generates significant uncertainty over how global change will impact forests. Thus, bringing together researchers who are tackling this pressing ecological challenge across diverse systems, orders of biological organization, and spatiotemporal scales is timelier than ever. In the spirit of this year’s meeting theme, “Change is Gonna Come”, it is fitting that the topic of this symposium seeks to address the impacts of future climate change on forest ecosystem function. The goal of this session is to synthesize and connect current work aimed at understanding drought and/or herbivore-induced tree defense mechanisms across multiple scales to better predict tree susceptibility to destructive herbivores and mortality. We will showcase transformative, cross-disciplinary approaches centered on explaining how and when drought and herbivores alter the production of defenses, the subsequent trade-offs that must occur, and the physiological and ecological consequences for tree survival and fitness. We hope this session will integrate approaches for understanding drivers of tree mortality by linking stress physiology with biotic attack through a deeper appreciation of tree metabolites.