Freshwater mussels (Order: Unionida) are among the most imperiled taxonomic groups in the United States; however, identifying locations of high diversity that warrant protection and locations suitable for population or habitat restoration is challenging. The Delaware River Basin (DRB) supports 13 freshwater mussel species that are exposed to multiple threats (e.g., urbanization, water withdrawals, and reservoir releases), which alter water quality, temperatures, and flow regimes, resulting in declines in the number of mussel populations. These declines— along with spatial variability in multiple, interacting stressors—make the DRB an ideal watershed to investigate locations of potential restoration actions. We first developed a joint species distribution model to 1) predict habitat suitability for mussel species in the basin, and 2) identify locations for restoration actions that maximize positive change to species habitat. We compiled mussel species presence/absence data from state and researcher databases and used landscape-scale environmental covariates (e.g., forested riparian area, stream slope, dam density) to predict mussel distributions. We then applied a multivariate hierarchical generalized linear mixed model with Bayesian inference to explain spatial variation in community composition within U.S. Environmental Protection Agency’s StreamCat catchments. We assessed spatial distribution in model uncertainty for variables representative of restoration actions (e.g., dam removal, water quality restoration, and increasing native vegetation) to determine which habitats may (or may not) improve for select assemblages. We then coupled the joint species distribution model with age-structured population dynamics and host-facilitated dispersal to identify catchments that may sustain reproducing populations of each species. These results were used to identify catchments within the DRB that are most likely to contain suitable release sites for hatchery-reared mussels, an important restoration tool. We demonstrate that a basin-wide framework that prioritizes across wide-ranging geographies and actions can maximize limited resources towards freshwater mussel conservation.