Ecosystems worldwide continue to experience rapid rates of habitat and species loss. Management actions to conserve and restore functional habitats are needed to reduce these declines, but funding and resources for such actions are limited. Spatial conservation prioritization (SCP) can facilitate strategic decision-making for targeted conservation planning and delivery, but complexities arise when management objectives include multiple wildlife species and ecological or management constraints, all of which can be further complicated by data uncertainty and existing conservation plans. The Prioritizing Restoration of Sagebrush Ecosystems Tool (PReSET), an R package-based decision-support tool, supports strategic ecosystem management planning across the sagebrush biome by using SCP. We adapted PReSET to better address the needs of multiple wildlife species, evaluate the effects of different ecological or management constraints on conservation outcomes, assess the influence of data uncertainty, and integrate existing conservation plans. Specifically, we developed optimization problems to identify priority sagebrush protection and restoration across the state of Wyoming, USA, and evaluated the efficacy and trade-offs of various approaches to problem design. We evaluated trade-offs in targeting multiple species compared to a single species, including using greater sage-grouse as a potential umbrella species to benefit other sagebrush-dependent wildlife. We then evaluated multi-species protection and restoration problems aimed at minimizing the risks of inadequate connectivity, climate change, and restoration failure, and accounted for data uncertainty to assess relationships between risk aversion of managers and conservation outcomes. We also developed optimization problems within conservation areas identified by an existing sagebrush conservation plan to evaluate the efficacy of guiding local-scale conservation delivery within more broadly defined conservation areas. Our results demonstrate how SCP methods can leverage novel spatial data to develop targeted decision-support resources that can facilitate landscape conservation planning and improve management outcomes across a wide array of systems and species.