Abstract Rapid environmental changes—in climate, land use, and biotic interactions—are accelerating species extinctions and extirpations globally. Identifying drivers that threaten populations is essential for conservation yet can be difficult given the variable nature of the response of an organism to biotic and abiotic stressors. We analyzed a long-term monitoring data set to explore demographic responses of fishers (Pekania pennanti) to rapid environmental change in the southern Sierra Nevada, California, United States. Fisher survival was sensitive to both biotic and abiotic factors, although the strength and direction of these effects were ultimately mediated by age and sex. Specifically, male survival was lower among young individuals and decreased with increasing temperatures and fungi consumption. Female survival was resilient to age effects and diet but increased with greater forest heterogeneity and decreased with increasing temperatures and snow depth. Our findings suggest that continued climate change will likely have consequences for fishers through both incremental stressors and extreme weather events, but increasing forest heterogeneity may help to buffer against the impacts of such change. Further, we illustrate the importance of disentangling the effects of intrinsic and extrinsic factors on survival, especially among species with distinct sexual or ontogenetic differences. As global drivers of environmental change intensify in strength and frequency, understanding these complex relationships will allow practitioners to best manage for population persistence and habitat resilience concurrently.