This chapter provides an in-depth exploration of contemporary therapeutic strategies in cancer treatment, emphasizing the potential of innovative genetic editing tools and drug repurposing methodologies. It begins with a thorough examination of meganucleases (MNs) and CRISPR-Cas systems, both of which have revolutionized genomic editing. These technologies allow for precise modifications of the genome, enabling targeted therapies that can directly address the genetic anomalies driving cancer progression. The application of these tools in oncology is discussed, showcasing their ability to disrupt cancerous growth at the molecular level. The chapter also delves into oncolytic virotherapy, an emerging field that leverages viruses that are genetically engineered to selectively infect and kill cancer cells while sparing normal tissues. Detailed case studies of Gendicine, Oncorine, and Imlygic illustrate the clinical successes and challenges associated with these therapies. These oncolytic viruses not only destroy cancer cells but also stimulate anti-tumor immune responses, offering a dual mechanism of action. Another significant focus of the chapter is on drug repurposing, a strategy that identifies new therapeutic uses for existing drugs, thus accelerating the development of cancer treatments. This approach is particularly advantageous as it utilizes drugs with known safety profiles, minimizing the cost and time before involving new treatment to the market. The chapter outlines the principles of drug repurposing, providing examples of repurposed drugs that have shown efficacy in treating various cancers. The initiatives led by the National Center for Advancing Translational Sciences (NCATS), are highlighted to underscore the institutional support for drug repurposing efforts. These initiatives aim to bridge the gap between laboratory discoveries and clinical applications, fostering innovation in cancer therapeutics. In summary, the chapter offers a comprehensive review of state-of-the-art cancer therapies, from cutting-edge genetic editing to the innovative repurposing of existing drugs, emphasizing their potential to transform the landscape of cancer treatment.