Large terrestrial carnivores are among some of the most threatened species, having experienced range contractions and population declines over the past two centuries. Factors such as habitat degradation and fragmentation and the direct killing of individuals pose significant risks to their survival. An understanding of the problem and factors affecting large mammal populations requires analysis at multiple scales to inform evidence-based decision making. The Andean bear (Tremarctos ornatus), South America's sole bear species and classified as vulnerable, confronts multiple threats including habitat loss, fragmentation, and illegal killing. At a local scale, I evaluated the effects of management, environmental, social, and economic variables on livestock losses caused by Andean bears, people's attitudes towards the presence of bears, and illegal killing of Andean bears; I compared, at multiple scales, the use of temporal replicates (camera traps) to spatial replicates (sign surveys) with respect to the precision of detection probability estimates and costs; I employed multi-scale occupancy models to evaluate drivers of Andean bear occupancy across most of Colombia, Ecuador, and Peru, including the effects of killing, natural area availability, and human presence; finally, on a regional scale, I evaluated the efficacy of alternative governmental zoning strategies for Andean bear conservation. The Andean bear faces significant challenges due to human persecution and habitat loss, underscoring the urgent need for comprehensive conservation efforts to ensure the survival of this iconic species in South America. My results support that 1) several of the existing protected areas in Colombia, Ecuador, and Peru have high Andean bear occupancy but fall short of adequately conserving populations due to their size and location limitations; 2) Core Conservation Units (COCOUNs) prove effective for conservation; consequently, 3) continuous evaluation and management of threats are essential to prevent fragmentation of the Andean bear's range, especially near roads, populated areas, and areas with hunting and extensive livestock farming; 5) government organizations responsible for Andean bears need mechanisms to improve the efficacy to attend and manage human-wildlife conflicts; 6) the appropriate management of Andean bear populations in key areas will allow for the long-term conservation of the species.