Targeted therapy has emerged as a promising option in cancer treatment, driven by advances in the understanding of DNA changes and the molecular basis of cancer. This article provides an overview of next-generation sequencing and types of genetic alterations, common cancer biomarkers, a review of circulating tumor DNA testing and its applications for oncology treatments, how to read a genomic testing report, examples of targeted therapy for cancer pathologic variants and tumor markers, and the implications for nursing practice in this emerging field.