Simple SummaryDiscovering new strategies for cancer treatment is critical, considering that each year millions of deaths are caused by this disease. In this sense, therapies based on nanomedicine are an innovative approach for cancer treatment, not only because they make it possible to perform targeted therapy, but also because they can improve patients’ quality of life. A key step to transfer new treatments from bench to beside is in vivo evaluation of a therapy, where zebrafish as a model organism has a fundamental role. Zebrafish has several benefits that make it ideal for studying the therapeutic capacity of novel nanotechnology-based anticancer therapies. In this review, we evaluate the potential of the nanomedicine and zebrafish synergy to achieve personalized treatments for cancer.Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specific cancer models. The role of zebrafish as a model for anticancer therapy studies has been highly evidenced, allowing researchers not only to perform drug screenings but also to evaluate novel therapies such as immunotherapies and nanotherapies. Beyond that, zebrafish can be used as an “avatar” model for performing patient-derived xenografts for personalized medicine. These characteristics place zebrafish in an attractive position as a role model for evaluating novel therapies for cancer treatment, such as nanomedicine.