Simple SummaryThe current article provides an overview of the significance of using various mouse and zebrafish models in cancer research. In addition, this review discusses an interdisciplinary ‘Team Medicine’ approach that has aided in enhancing our understanding of carcinogenesis and establishing new therapeutic approaches. The biological course of human malignancies, preclinical research on prospective cancer treatments, and cancer prevention benefit significantly from experimental animal models. The molecular mechanisms underlying tumor growth, progression, metastasis, maintenance, and acquisition of chemo-resistance have received significant attention in the study using different types of mice cancer models. Zebrafish have been recommended as a potential model to investigate human cancer because of their suitability for in vivo imaging, fast development, chemical screening, and adaptable genetics. The zebrafish’s forward genetics and vertebrate biology make it a model system with immense potential for understanding carcinogenesis. The significance of applying various animal models in studying cancer development and progression has been well proven. The current review provides a comprehensive description of how these diverse models may be applied productively based on the scientific challenges that need to be addressed.AbstractAnimal models have been utilized for decades to investigate the causes of human diseases and provide platforms for testing novel therapies. Indeed, breakthrough advances in genetically engineered mouse (GEM) models and xenograft transplantation technologies have dramatically benefited in elucidating the mechanisms underlying the pathogenesis of multiple diseases, including cancer. The currently available GEM models have been employed to assess specific genetic changes that underlay many features of carcinogenesis, including variations in tumor cell proliferation, apoptosis, invasion, metastasis, angiogenesis, and drug resistance. In addition, mice models render it easier to locate tumor biomarkers for the recognition, prognosis, and surveillance of cancer progression and recurrence. Furthermore, the patient-derived xenograft (PDX) model, which involves the direct surgical transfer of fresh human tumor samples to immunodeficient mice, has contributed significantly to advancing the field of drug discovery and therapeutics. Here, we provide a synopsis of mouse and zebrafish models used in cancer research as well as an interdisciplinary ‘Team Medicine’ approach that has not only accelerated our understanding of varied aspects of carcinogenesis but has also been instrumental in developing novel therapeutic strategies.