Simple SummaryAppropriate testing models are imperative to facilitate the discovery of effective personalized treatments against different cancers, including advanced cervical cancer. This review provides a comprehensive overview of the currently available three-dimensional (3D) models of cervical cancer and their significance in pre-clinical and clinical studies. The review emphasizes the potential of 3D tumor models, such as spheroids from cervical cancer cell lines and patient-derived organoids, to evaluate novel therapies, particularly immunotherapies that target tumor cells and modulate the tumor microenvironment. Notably, the cervical cancer field is underdeveloped regarding use of 3D tumor models, and there is an increasing need to develop appropriate models to address this clinical burden, which will aid in personalized treatment discovery.AbstractCervical cancer is one of the most common malignant diseases in women worldwide. Despite the global introduction of a preventive vaccine against the leading cause of cervical cancer, human papillomavirus (HPV) infection, the incidence of this malignant disease is still very high, especially in economically challenged areas. New advances in cancer therapy, especially the rapid development and application of different immunotherapy strategies, have shown promising pre-clinical and clinical results. However, mortality from advanced stages of cervical cancer remains a significant concern. Precise and thorough evaluation of potential novel anti-cancer therapies in pre-clinical phases is indispensable for efficient development of new, more successful treatment options for cancer patients. Recently, 3D tumor models have become the gold standard in pre-clinical cancer research due to their capacity to better mimic the architecture and microenvironment of tumor tissue as compared to standard two-dimensional (2D) cell cultures. This review will focus on the application of spheroids and patient-derived organoids (PDOs) as tumor models to develop novel therapies against cervical cancer, with an emphasis on the immunotherapies that specifically target cancer cells and modulate the tumor microenvironment (TME).