His research is related to computer science and its applications, the development of algorithms and data analysis solutions, and open infrastructure and services. The created software has enabled discoveries in biology, such as regarding the regulation and function of genes, the work of receptors, and the analysis of the links between various omics and diseases, as well as contributed to the research of other scientists. He has also compiled glossaries and promoted Estonian language technology for over ten years. Vilo has brought dozens of international grants to Estonia and led more than 70 projects.

Jaak Vilo has been awarded the Estonian Order of the White Star, 3rd class, and the University of Tartu Medal. The Minister for Education and Research has given him letters of appreciation for the research awards for supervised students. In 2013, he was named Person of the Year by the Estonian Association of Information Technology and Telecommunications. In 2020, the Association for Computing Machinery gave him the status of a senior member.