Conservation lands face a mounting threat of ecosystem transformation and the loss of biodiversity from the invasion of fire-prone perennial and annual grasses. Managers must make difficult decisions to find efficient ways to expend limited resources to manage large and complex landscapes amidst substantial uncertainty regarding effective treatment strategies, climates, and invader-induced novel processes. We developed a state-and-transition simulation model coupled with a fire behavior model to study impacts to native biodiversity and fire regimes in a national park invaded by a perennial grass. We evaluated resources required to meet management objectives, and how to spatially allocate available resources efficiently and effectively. Management strategies and ecological scenarios strongly influenced the ability to minimize potential impacts; the inclusion of a new management strategy, aerial precision spot spraying targeting low cover levels in remote regions, was needed to supplement current treatments that can only target large, dense patches. Adding this new treatment method may be enough to conserve the desert ecosystem from small scale transformation through invasive competition and from broad functional transformations through invasive-induced fire regime changes. Spot spraying may also be highly beneficial if wetter monsoonal conditions create faster growth rates, decreasing the ability to contain the invasion even with unlimited management resources. Given current annual budgets for control, and the new treatment option, invasion control and preservation of native biodiversity may be possible regardless of spatial prioritization. Coupled empirical and process-based models efficiently simulated the effects of management activities, quantifying potential management costs and ecological impacts, while considering a wide range of possible future uncertainties associated with climate, spread rates, and wildfires lacking historical precedent. These techniques could be applied to other situations to evaluate the feasibility of conservation goals and to determine actions that would be most efficient and effective in meeting those goals.