Animal and plant species often face multiple threats simultaneously. We explored the relative impact of three major threats on populations of the endangered San Joaquin kit fox. This species was once widely distributed across the southern San Joaquin Valley, California, USA, but agriculture and urban development have replaced much of its natural habitat. We modeled impacts of climate change, land-use change, and rodenticide exposure on kit fox populations using a spatially explicit, individual-based population model from 2000 to 2050 for the Central Valley, California. Our study indicates that land-use change will likely have the largest impact on kit fox populations. Land development has the potential to decrease populations by approximately 15% under a compact growth scenario in which projected population increases are accommodated within existing urban areas, and 17% under a business-as-usual scenario in which future population growth increases the developed area around urban centers. Plausible scenarios for exposure to pesticides suggest a reduction in kit fox populations by approximately 13%. By contrast, climate change has the potential to ameliorate some of these impacts. Climate-change induced vegetation shifts have the potential to increase total available kit fox habitat and could drive population increases of up to 7%. These vegetation shifts could also reduce movement barriers and create opportunities for hybridization between the endangered San Joaquin kit fox and the more widely distributed desert kit fox, found in the Mojave Desert. In contrast to these beneficial impacts, increasing climate extremes raise the probability of the kit fox population dropping below critical levels. Taken together, these results paint a complex picture of how an at-risk species is likely to respond to multiple threats.