Abstract With the progression of modern information techniques, such as next generation sequencing (NGS), Internet of Everything (IoE) based smart sensors, and artificial intelligence algorithms, data-intensive research and applications are emerging as the fourth paradigm for scientific discovery. However, we face many challenges to practical application of this paradigm. In this article, 10 challenges to data-intensive discovery and applications in precision medicine and healthcare are summarized and the future perspectives on next generation medicine are discussed.