Targeting conservation actions efficiently requires information on vulnerability of and threats to conservation targets, but such information is rarely included in conservation plans. In the U.S., recently updated State Wildlife Action Plans identify Conservation Opportunity Areas (COAs) selected by each state as priority areas for future action to conserve wildlife and habitats. The question is how threatened these COAs are by habitat loss and degradation, major threats to wildlife in the U.S. that are often caused by housing development. We compiled spatial data on COAs across the conterminous U.S. We estimated COA vulnerability using current land protection status and COA threat using projected housing growth derived from U.S. census data. COAs comprise 1–46% of each region. Across regions, 28–82% of the area within COAs is vulnerable to future housing development, and 5–55% and 7–23% of that vulnerable COA area is threatened by projected dense housing and rapid housing growth, respectively. COA vulnerability is greatest in the East. Threat from dense housing and rapid housing growth is highest in the Northeast and Pacific Southwest, respectively. Results highlight that many areas identified as important for reducing wildlife listings under the U.S. Endangered Species Act may need further protection to fulfill their conservation goals because they are both vulnerable to and threatened by future housing development. Our analyses can help practitioners target local government outreach, land protection efforts, and landscape-scale mitigation programs to decrease future COA loss from housing development, and could be expanded to address additional COA threats (e.g., wildfire, invasive species).