Cancer is caused by defective gene, and those mutations may cause tumorigenesis. As new drugs could lead to new paths of resistance also, cancer therapy seems like an endless battle today. The concept of gene therapy as a way to treat diseases that were thought to be difficult or incurable has been around for about three decades. A gene therapy involves replacing a defective or missing gene with a normal copy to correct a genetic defect. This therapy has become one of the most promising treatments for cancer due to technological and scientific advancements over the past decade. A number of gene therapy approaches have been developed, including the use of cancer suppressor gene therapy, oncogene silencing, suicide gene therapy, and gene-editing techniques. Primary and disseminated tumors can be treated with gene therapy without harming normal cells, but delivering genes has always been a controversial process. Therefore, different types of carriers are being explored for gene transfer. The chapter aims to present recent advances in gene therapy strategies, delivery mechanisms, and reported clinical trials.