<p>Ovarian cancer (OC) is one of the most common malignancies of the female reproductive system. It is highly heterogeneous and ranks the fifth most prevalent cancer worldwide. Most patients are diagnosed at an advanced stage, resulting in low survival rates and poor prognosis. Recent advances in whole-exome sequencing techniques have revealed that abnormalities in DNA double-strand break (DSB)-related genes are closely linked to OC development. DSBs are a severe form of DNA damage that poses a significant threat to cellular stability. Their programmed formation, along with the two primary DSB repair mechanisms—homologous recombination repair and non-homologous end-joining repair—are essential during meiosis, facilitating genetic exchange and recombination between homologous chromosomes. Fine regulation of these pathways ensures genomic stability and the accurate transmission of genetic information. Numerous genes are involved in regulation and repair of programmed DSBs. Mutations or aberrant expression of these genes can disrupt the repair mechanisms, contributing to development of malignancies such as OC. This review examines the role of DSB-related genes in OC pathogenesis and summarizes novel therapeutic strategies targeting these mechanisms, offering new insights into OC development and treatment.</p>