Contemporary patterns of species decline frequently stem from multiple, synergistic pressures, which much like the genetic concept of lethal equivalents, must be interpreted in sum rather than as independent deleterious entities. For example, the recent, range-wide decline of the Allegheny woodrat (Neotoma magister) is likely a result of numerous, minor, human-mediated stressors including habitat fragmentation and disruption of metapopulation dynamics, reduced hard mast availability associated with the functional extirpation of American chestnut (Castanea dentata) and recent shifts in forest composition, and expansion of a human-adapted species, the raccoon (Procyon lotor) and the parasites it carries (Baylisascaris procyonis). To evaluate the assertion that range-wide woodrat declines have been caused by a concatenate of stressors, we used principal component (PC) analysis to identify latent relationships among a suite of biological and ecological factors (reflecting those stressors listed above) and evaluated PC scores relative to the three conservation states of woodrat populations in Indiana (stable, diminished and extirpated). Populations of differing conservation states segregated along each of the three retained PCs, providing support for the assertion that a combination of stressors has contributed to the range-wide decline of woodrat metapopulations, although intriguingly, independent stressors appeared to cause the decline of individual populations. These results suggest specific, minimal site attributes must be met for each of the habitat attributes evaluated to support stable woodrat populations. Our findings further suggest that variation in relative pressures exerted by individual stressors across populations will require site-specific management actions if woodrat populations are to be recovered throughout their range. Our case study of Indiana woodrats exemplifies the first step in identifying site-specific causes for species’ declines, necessary to guide subsequent management and recovery actions when a combination of interwoven factors likely are contributing to metapopulation degeneration.