Ovarian cancer is the leading cause of death among women with gynecological cancer, with an overall 5-year survival rate below 50% due to a lack of specific symptoms, late stage at time of diagnosis and a high rate of recurrence after standard therapy. A better understanding of heterogeneity, genetic mutations, biological behavior and immunosuppression in the tumor microenvironment have allowed the development of more effective therapies based on anti-angiogenic treatments, PARP and immune checkpoint inhibitors, adoptive cell therapies and oncolytic vectors. Oncolytic adenoviruses are commonly used platforms in cancer gene therapy that selectively replicate in tumor cells and at the same time are able to stimulate the immune system. In addition, they can be genetically modified to enhance their potency and overcome physical and immunological barriers. In this review we highlight the challenges of adenovirus-based oncolytic therapies targeting ovarian cancer and outline recent advances to improve their potential in combination with immunotherapies.