Cancer gene therapy has rapidly evolved from experimental development into clinically validated treatment modalities, offering new opportunities in the fight against cancer. This chapter highlights advances in gene-editing technologies such as CRISP-Cas9, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), which target cancer-related mutations and immune evasion pathways, addressing key cancer hallmarks. Chimeric antigen receptor (CAR) T-cell therapies highlight the success of ex vivo gene editing, moving toward more accessible and personalized cancer treatments. Moreover, strategies like suicide gene therapy (SGT) and cytokine gene therapy further demonstrate the versatility in modulating tumor microenvironment (TME) for therapeutic purposes. Challenges remain in safe and efficient gene delivery with widely used viral vectors presenting risks like immunogenicity, while nonviral delivery systems offer safer alternatives. Continued innovation in gene delivery, regulation, and combination therapies is essential for improving the precision and scalability of cancer gene therapy. This chapter concludes by discussing the future directions, emphasizing research aimed at optimizing genome editing and delivery methods to minimize off-target effects and their widespread clinical use. As understanding about those mechanisms and strategies advances, cancer gene therapy holds great promise for personalized and precision oncology, tailored to the unique makeup of individual tumors.