Landraces and indigenous varieties comprise valuable sources of crop species diversity. Their utilization in plant breeding may lead to increased yield and enhanced quality traits, as well as resilience to various abiotic and biotic stresses. Recently, new approaches based on the rapid advancement of genomic technologies such as deciphering of pangenomes, multi-omics tools, marker-assisted selection (MAS), genome-wide association studies (GWAS), and CRISPR/Cas9 gene editing greatly facilitated the exploitation of landraces in modern plant breeding. In this paper, we present a comprehensive overview of the implementation of new genomic technologies and highlight their importance in pinpointing the genetic basis of desirable traits in landraces and indigenous varieties of annual, perennial herbaceous, and woody crop species cultivated in the Mediterranean region. The need for further employment of advanced -omic technologies to unravel the full potential of landraces and indigenous varieties underutilized genetic diversity is also indicated. Ultimately, the large amount of genomic data emerging from the investigation of landraces and indigenous varieties reveals their potential as a source of valuable genes and traits for breeding. The role of landraces and indigenous varieties in mitigating the ongoing risks posed by climate change in agriculture and food security is also highlighted.