Wheat (Triticum aestivum L.) is a widely consumed staple crop and essential component of a healthy whole-grain diet. One component of wheat, fructans, is known to serve physiological roles in the plant and confer health benefits to humans. Fructans serve as reserve carbohydrates and osmotic regulators against stresses (i.e., drought, cold temperatures, and salinity) that affect grain yield in the wheat plant. For humans, fructans are prebiotics that promote growth of healthy gut bacteria, aid in immune support, reduce colon cancer incidence, and support bone health. Given the roles of fructans in plant and human physiology, breeding for wheat grain fructan content would produce climate resilient, nutritionally improved varieties Breeding for nutritional traits is a long-term, resource intensive process. Genomic Selection (GS) could help accelerate the breeding process while decreasing phenotyping requirements. This work focused on key issues surrounding the implementation of GS for wheat grain fructan content. First, the existence of genotype-by-environment (GxE) interactions and impacts of interactions on genomic selection (GS) was examined for grain fructan content. Second, the underlying genetic architecture of wheat grain fructan content was examined to determine the feasibility of implementing genomic selection (GS). Lastly, two GS selection methodologies were compared in terms of realized gain from selection for grain fructan content, and impacts on inbreeding, genetic variance, and agronomic characteristics. The key messages of these studies are 1) GxE interactions do exist for wheat grain fructan content, but their impacts on GS prediction accuracies is small, 2) the underlying genetic architecture of wheat grain fructan content supports the use of GS methodologies, 3) GS for wheat grain fructan content is a feasible, effective selection methodology which produces significant gains from selection, 4) the use of Optimum Contribution Selection (OCS) to control for long term inbreeding does effectively control inbreeding and better conserve genetic variance relative to GBLUP selection populations. Breeding programs implementing GS for wheat grain fructan content should focus their efforts on designing breeding pipelines to capitalize on varying maturity of crossing materials, controlling inbreeding within populations, updating training populations often, and evaluation of materials over multiple years of field trials.