Abstract Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are transformative next-generation sequencing (NGS) technologies that have rapidly revolutionized clinical diagnostics, particularly in cases of rare genetic disorders and oncology. WGS provides comprehensive data by covering the entire genome, including coding and noncoding regions, allowing single-nucleotide variants, small insertions/deletions, structural variants, and copy number variations to be detected. Conversely, WES targets the protein-coding exome, which represents only 1%–2% of the genome yet contains approximately 85% of the pathogenic mutations. This review discusses the technological underpinnings, clinical applications, challenges, and future prospects of WGS and WES. We explored their roles in rare disease diagnosis, personalized cancer therapy guidance, neonatal screening, pharmacogenomics, and reproductive carrier screening. Despite significant advancements, challenges remain in data interpretation, computational requirements, cost-effectiveness, ethical issues, and clinical integration. Advances in long-read sequencing, artificial intelligence–assisted interpretation, multi-omics integration, and supportive policy initiatives that aim to broaden access to precision medicine are warranted.
Chen et al. (2026) studied this question.