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The Amur tiger and leopard, once roaming over the Eurasian continent, are now endangered and confined to the Sikhote-Alin Mountains, Russia—a landscape that has been increasingly fragmented due to human activities. The ultimate fate of these big cats depends on whether they can resettle in their previous main historical range in NE China. Recent sightings of these animals along the China–Russia border have aroused new hope, but direct evidence is lacking. The main objectives of our study were (1) to determine the abundance and spatiotemporal patterns of tigers, leopards, and primary prey; (2) to investigate factors influencing the resettlement of the two big cats; and (3) to propose a landscape-scale conservation plan to secure the long-term sustainability of the Amur tiger and leopard. We monitored the two felids, their prey, and human activities, with 380 camera-trap stations, for a total of 175,127 trap days and over an area of 6000 km2 in NE China. We used the constraint line method to characterize cattle grazing and human influences on tigers, leopards, and their prey species. Our results show that, unexpectedly, at least 26 tigers and 42 leopards are present within China, which are confined primarily to a narrow area along the border with Russia. We have further identified that cattle grazing and human disturbances are the key hurdles to the dispersal of the tigers and leopards farther into China where suitable habitat is potentially available. Amur tigers and leopards are returning to China, indeed, but their long-term resettlement is not likely without active and timely conservation efforts on landscape and regional scales. To overcome the hurdles to the resettlement of tigers and leopards in China, we propose a “Tiger and Leopard Resettlement Program” that will engage the government, local communities, and researchers, so that the long-term sustainability of the Amur tigers and leopards can be ensured.