Objective To develop an interdisciplinary nursing informatics course and apply project-based learning to enhance information skills among undergraduate students. Methods A total of 48 undergraduate students were divided into an intervention group and a control group, each consisting of 24 students. The intervention group received an interdisciplinary course structure with integrated online modules, enabling a blended online-offline, project-based learning experience. A mixed-methods approach was used to evaluate the course′s effectiveness. Results After the course, computer attitude scores in the intervention group were significantly higher than those in the control group (P<0.05). Interviews with selected students from the intervention group indicated that the course deepened their understanding of nursing informatics and interdisciplinary research and improved their ability to use information technology to solve nursing challenges. Conclusion Project-based learning in nursing informatics can enhance students′ attitudes toward information technology use and strengthen their practical skills.