BACKGROUND/OBJECTIVE: Omics technology has become a widely applied biological science that can be used to study the etiology, pathogenesis, and treatment of osteosarcoma(OS). Bibliometric analysis is still blank in this field.This study aimed to access the trends and hotspots of omics in OS research through the bibliometric analysis method. METHODS: Relevant articles and reviews from 1999 to 2023 were retrieved from the Web of Science Core Collection. The data were processed with CiteSpace, and some graphs were generated with Graphpad, VOSviewer, Scimago Graphica, Bibliometrix and R Studio. RESULTS: A total of 1581 papers were included. China (569, 36.0%) and the United States (523, 33.1%) took the dominant position in the number of published papers, and the links between countries most frequently occurred between North America and East Asia, and between Australia and Europe. Top institutions with the highest number of publications were almost located in the United States, with The University of Texas MD Anderson Cancer Center contributing the most (44, 2.78%). Among the researchers in this field, Cleton-Jansen AM was the author with the highest number of articles in the field (20, 1.27%). According to the keyword cluster analysis, most studies focused on the "comparative genomic hybridization" before 2012. The latest surge words "tumor microenvironment" and "immune infiltration" in the keyword heatmap indicate future research directions. CONCLUSION: Our study provided the current status of the omics research in OS on a global level and the hottest directions. The field of omics in OS was developing rapidly, and the main focuses of research were revealing the characteristics of tumor microenvironment of OS and how to activate the immune system to fight cancer cells. Research on the immune microenvironment and its relationship with genetic aberrations of OS will be a priority in the future.