Habitat loss and fragmentation are major drivers of biodiversity loss, with large carnivores being particularly vulnerable due to their large home ranges. These species were once widespread across the African continent but over the past 100 years their ranges have decreased by more than 75% and there is continued pressure on the remaining free-roaming populations. In South Africa (SA) the land management strategy that includes fencing of wildlife has restricted African lion (Panthera leo) and African wild dog (Lycaon pictus) to protected areas (state and private). This resulted in increasingly small, isolated population islands surrounded by a sea of anthropogenically-transformed landscapes resistant to carnivore dispersal. SA has three of the IUCN-proposed Lion Conservation Units in large Transfrontier Parks and Conservation Areas; in addition, approximately 800 lions in 47 smaller, fenced reserves also hold conservation value. Wild dog populations historically have been small and patchy but Ne has been further reduced and isolation increased by human impacts. Despite high mobility and long-distance dispersal, SA wild dogs are genetically differentiated from East Africa, separated by a large zone of admixture. In the late 1990's a managed metapopulation approach was adopted to mimic natural processes and connectivity of wild dog populations. The current SA managed metapopulation comprises 19 packs in 11 reserves. A similar approach has been adopted for lions more recently. We demonstrate how inferences from genetic data provide perspectives across multiple temporal and spatial scales, to inform this managed metapopulation approach and to contribute to long-term species viability of large carnivores.