Interleukin-12 (IL-12) is a potent immunostimulatory cytokine with demonstrated antitumor properties, yet its clinical translation is limited by systemic toxicity when using recombinant protein. This chapter provides an overview of IL-12 gene therapy approaches with an emphasis on preclinical, veterinary, and human clinical studies using various delivery platforms, including cell-based vectors, oncolytic viruses, gene electrotransfer (GET), and lipid-based or chemical carriers. Across diverse tumor models, these strategies have shown promise in enhancing local IL-12 expression, activating innate and adaptive immunity, and achieving significant tumor control. GET, in particular, has emerged as a highly effective and clinically translatable method due to its precision, safety, and capacity for combination with other modalities. This chapter highlights the immunological mechanisms, therapeutic outcomes, and translational potential of IL-12 gene therapy across different delivery systems.