This work describes the application of genomics towards improving fruit quality traits in a winter squash breeding program and elucidating the genetics of squash fruit quality. Phenotypes related to fruit quality can only be assessed at the end of the growing season and are laborious to measure. Squash are demanding in terms of space, which greatly reduces breeding population sizes in the field and in the greenhouse relative to other crops. These constraints motivated an investigation into the use of genomic selection to reduce breeding cycle length and enable earlier selection. Initial work was conducted to determine the prediction accuracy of different modeling approaches for key fruit traits; accuracies were deemed sufficient for deployment for all traits of interest. A selection experiment was then conducted using index selection facilitated by a multi-trait GBLUP model to improve three fruit quality traits: degree Brix, %dry matter, and color value a*. An evaluation of this selection experiment revealed significant genetic gain in all three traits and total index value. To compliment applied breeding work, an RNA-Seq experiment was conducted in several cultivars of varying fruit quality. Gene expression data indicated that differential gene expression may explain some of the observed phenotypic variation, and suggested candidate genes for further investigation.