Maximising conservation outcomes for threatened species in multi-use landscapes is likely to require a multi-stakeholder, coordinated approach that is tenure blind. Here, we conduct a review of a research program targeting the endangered northern quoll (Dasyurus hallucatus) in the Pilbara region of Western Australia; an area with a high concentration of mining and pastoral activities. To inform ongoing investment to support northern quoll conservation, we identify future directions that either add value to research already undertaken or are based on the original priorities that have not been addressed. The original program was developed using a collaborative process involving workshops attended by multiple stakeholders to identify research priorities. To date, the program has significantly improved our knowledge of Pilbara northern quolls, particularly in relation to effective survey and monitoring techniques, the influence of habitat quantity, configuration, and composition on occupancy, movement ecology, population dynamics and structure, and the threat posed by introduced predators. The efficacy of artificial refuges that were created to replicate natural denning habitat has also been investigated. Suggested future research directions focus on refining the northern quoll regional monitoring program, understanding how interacting threats such as introduced predators, fire, and herbivore grazing influence northern quoll populations in the Pilbara, and how best to mitigate other threats such as mining associated activities and the impending cane toad invasion.