Multi-material additive manufacturing of polymers has experienced a remarkable increase in interest over the last 20 years. This technology can rapidly design and directly fabricate three-dimensional (3D) parts with multiple materials without complicating manufacturing processes. This research aims to obtain a comprehensive and in-depth understanding of the current state of research and reveal challenges and opportunities for future research in the area. To achieve the goal, this study conducts a scientometric analysis and a systematic review of the global research published from 2000 to 2021 on multi-material additive manufacturing of polymers. In the scientometric analysis, a total of 2512 journal papers from the Scopus database were analyzed by evaluating the number of publications, literature coupling, keyword co-occurrence, authorship, and countries/regions activities. By doing so, the main research frame, articles, and topics of this research field were quantitatively determined. Subsequently, an in-depth systematic review is proposed to provide insight into recent advances in multi-material additive manufacturing of polymers in the aspect of technologies and applications, respectively. From the scientometric analysis, a heavy bias was found towards studying materials in this field but also a lack of focus on developing technologies. The future trend is proposed by the systematic review and is discussed in the directions of interfacial bonding strength, printing efficiency, and microscale/nanoscale multi-material 3D printing. This study contributes by providing knowledge for practitioners and researchers to understand the state of the art of multi-material additive manufacturing of polymers and expose its research needs, which can serve both academia and industry.