Abstract: OBJECTIVE To study of the dynamic evolution process of the themes of off-label drug use from a macroscopic perspective, perspective is needed to reveal the overall development vein of the field, and discover research hot spots and development trends of the field. METHODS A total of 3 876 literatures published in Web of Science from 2012 to 2022 on the topic of off-label drug use were used to obtain three visual maps of overlapping map, systematic evolution map and strategic map by using SciMAT analysis, and these maps of each period were analyzed. RESULTS Over the past ten years, there had been an increasing in the number of publications, themes, and keywords on the off-label drug use, with research themes from the former period having a large impact on the latter period, with complex evolutionary pathways and increasing evolutionary themes. Roughly, 14 evolutionary paths were formed in 4 research directions:adolescents and children, treatment, off label use, and drug RCT. CONCLUSION The content and scope of research in the field of off-label drug use will be diversified and developed, with greater focus on pediatric drug use, psychiatric drug use, COVID-19, and guidelines will be paid more attention.