Demographic trends and changes to climate require a more efficient use of plant genetic resources in breeding programs. Indeed, the release of high-yielding varieties has resulted in crop genetic erosion and loss of diversity. This has produced an increased susceptibility to severe stresses and a reduction of several food quality parameters. Next generation sequencing (NGS) technologies are being increasingly used to explore “gene space” and to provide high-resolution profiling of nucleotide variation within germplasm collections. On the other hand, advances in high-throughput phenotyping are bridging the genotype-to-phenotype gap in crop selection. The combination of allelic and phenotypic data points via genome-wide association studies is facilitating the discovery of genetic loci that are associated with key agronomic traits. In this review, we provide a brief overview on the latest NGS-based and phenotyping technologies and on their role to unlocking the genetic potential of vegetable crops; then, we discuss the paradigm shift that is underway in horticultural crop breeding.