Cancer gene therapy has developed from relatively simple strategies for replacing defective genes into a broad therapeutic discipline that includes gene addition, gene silencing, suicide-gene therapy, oncolytic virotherapy, immunomodulatory gene transfer, RNA therapeutics, programmable genome and epigenome editing, and genetically engineered immune cells. The biological rationale is to exploit molecular abnormalities that distinguish malignant cells from normal tissues while using genetic payloads to restore tumor-suppressive functions, suppress oncogenic dependencies, trigger selective cytotoxicity, remodel the tumor microenvironment, or enhance antitumor immunity. This review critically examines the major cancer gene therapy strategies, their molecular mechanisms, delivery platforms, clinical development, advantages, and limitations. Tumor-suppressor replacement, particularly adenoviral TP53 delivery, established an important proof of concept for restoring a lost cellular checkpoint, whereas antisense oligonucleotides, small interfering RNAs, microRNA-based approaches, and CRISPR interference provide increasingly programmable methods for suppressing oncogenic signaling. Suicide-gene systems such as herpes simplex virus thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine exploit selective intracellular conversion of prodrugs and can generate bystander killing. Oncolytic viruses combine tumor-selective replication with direct lysis, antigen release, innate immune activation, and delivery of therapeutic transgenes; recent engineering approaches increasingly arm viruses with cytokines, immune agonists, or other payloads. Immunomodulatory gene therapy seeks to increase local cytokine activity, antigen presentation, costimulation, or chemotactic recruitment while limiting systemic toxicity. RNA therapeutics and lipid nanoparticle technologies provide transient, potentially repeatable delivery, whereas CRISPR/Cas systems, base editors, prime editors, and epigenome editors enable increasingly precise modification of endogenous genetic programs. Ex vivo genetic engineering of T cells, natural killer cells, and other immune effectors has already produced clinically established cancer therapies, while in vivo genome editing remains an important translational frontier. Despite substantial progress, efficacy is constrained by tumor heterogeneity, inadequate delivery to solid tumors, extracellular and intracellular barriers, antiviral immunity, off-target activity, genomic instability, antigen escape, immune suppression, manufacturing complexity, and cost. Current development is therefore moving toward biomarker-guided patient selection, tumor-restricted expression, transient or controllable editing, multiplex engineering, improved non-viral delivery, and rational combinations with checkpoint inhibitors, radiotherapy, chemotherapy, targeted agents, and other cell therapies. Overall, cancer gene therapy is evolving from a collection of individual technologies into an integrated precision-oncology platform in which the therapeutic payload, delivery system, target cell, and treatment context are designed as a single intervention.