The Science Framework for the Conservation and Restoration Strategy of the Department of the Interior, Secretarial Order 3336 (SO 3336), Rangeland Fire Prevention, Management and Restoration, provides a strategic, multiscale approach for prioritizing areas for management and determining effective management strategies across the sagebrush biome. The emphasis of this version is on sagebrush ecosystems and greater sage-grouse. The Science Framework uses a six step process in which sagebrush ecosystem resilience to disturbance and resistance to nonnative, invasive annual grasses is linked to species habitat information based on the distribution and abundance of focal species. The predominant ecosystem and anthropogenic threats are assessed, and a habitat matrix is developed that helps decision makers evaluate risks and determine appropriate management strategies at regional and local scales. Areas are prioritized for management action using a geospatial approach that overlays resilience and resistance, species habitat information, and predominant threats. Decision tools are discussed for determining the suitability of priority areas for management and the most appropriate management actions at regional to local scales. The Science Framework and geospatial crosscut are intended to complement the mitigation strategies associated with the Greater Sage-Grouse Land Use Plan amendments for the Department of the Interior Bureaus, such as the Bureau of Land Management, and the U.S. Forest Service.