The DARPA Reefense program seeks to create self-repairing, hybrid reef-mimicking structures to protect both civilian and Department of Defense infrastructure along coastlines. An adaptive biology component of this effort focuses on genomic selection to boost oyster resilience against dermo disease by 20% and enhance growth rates by 15%. Initial broodstock oysters were sourced from wild populations in St. Andrew Bay, Florida, and an existing aquaculture line representing populations from Louisiana, Alabama, Florida, and Texas (LAFT). These oysters were subjected to laboratory dermo challenges for both phenotypic and genomic selection, with genomic estimated breeding values (GEBVs) generated from the relationship between single nucleotide polymorphisms (SNPs) and dermo resistance. The Florida broodstock was used to produce a genomically selected line using the top GEBVs, a phenotypically selected line using traditional phenotypic performance, and a genomic control using oysters with average GEBVs. A fourth genomically selected line was produced from the LAFT line. All lines were deployed at sites in Alabama, Louisiana, and Florida, but the LAFT line was not permitted in Florida due to regulatory restrictions. Growth and survival was monitored monthly and dermo infection assessed quarterly. Growth varied among sites, but not among lines except the LAFT line generally grew faster as the only F1 line selected for faster growth. Field survival varied among sites related to differences in environmental condition, stock origin, and dermo pressure. In contrast, lab-based dermo challenges clearly indicated that the genomically selected FL oysters displayed higher dermo resistance compared to controls, while the LAFT line showed the least resistance. Results from the lab challenge and growth metrics informed a second round of GEBV calculations that were used to select broodstock for F2 production. In the F2 generation, the LAFT line was replaced with a wild control using oysters collected from the original St Andrew Bay population and is currently undergoing the same field challenges. Lab challenges to dermo were completed in July 2024 and demonstrated significantly greater survival in selected lines ranked as follows: genomically selected (79%) > phenotypically selected (51%) = genomic control (43%) > wild control (22%). Although field trials are not complete, lab challenge results were used to inform the selection of an F3 generation. Field performance is confounded by many other factors affecting survival in addition to disease yet results clearly indicate the improved performance provided by genomic selection.