There is a lack of studies to determine if avatar-based protocols could be considered an efficient and accurate strategy to improve psychological well-being in oncology patients, even though it represents a growing field of research. To the best of our knowledge, this is the first systematic review addressing the effectiveness of avatar-based treatments to enhance quality of life (QoL) and psychological well-being in breast cancer patients. The purpose of this study was to review the scientific literature of those studies involving avatar-based technology and breast cancer patients in order to answer the following questions. (1) Are avatar-based strategies useful to im-prove QoL and psychological well-being (anxiety and depression symptoms) in breast cancer patients? (2) Which is the best way to develop avatar-based protocols for breast cancer patients? We conducted a systematic review of the peer-reviewed literature from EBSCO, Ovid, PubMed, Scopus, and Web of Science (WOS), following the PRISMA statements and using “avatar + breast cancer” or “avatar + cancer” as keywords. Studies which were published in either English or Spanish and which addressed QoL and psychological well-being in breast cancer patients were reviewed. The results will contribute to developing innovative avatar-based strategies focused on breast cancer patients.