This study developed a STEAM (Science, Technology, Engineering, Art, and Math)-6E (Engage, Explore, Explain, Extend, Enrich, Evaluate; 6E Learning by Design) special course based on the theme of creative design of IoT (Internet of Things) assistant devices for the elderly and investigated the impact of this course on students’ learning effectiveness. It invited eight experts and scholars for focus interviews, jointly developed the STEAM-6E special course, designed teaching activities around the theme of creative design of IoT assistant devices for the elderly, and created a learning effectiveness scale. Furthermore, it selected 46 students majoring in nursing in a vocational and technological college as its subjects and distributed copies of a questionnaire among them to explore learning effectiveness. This study reached the following conclusions. The STEAM-6E special course on the creative design of IoT assistant devices for the elderly included three dimensions, that is, the STEAM course, 6E teaching, and the acquisition of professional knowledge, as well as 17 competence indicators. The nursing students affirmed the learning outcome in the STEAM-6E course, the 6E teaching model, and thematic knowledge after attending the STEAM-6E course. The hands-on activities of the STEAM-6E special course could guide students to learn key points step by step. The STEAM-6E special course can strengthen students’ abilities to integrate STEAM knowledge and improve their learning effectiveness in each discipline. The STEAM-6E special course for the elderly improved the cooperative learning, professional knowledge, and confidence of the students. In light of these conclusions, this study developed a teaching model for the STEAM-6E special course on the creative design of IoT assistant devices for the elderly and proposed several suggestions for curriculum planning and the implementation of a STEAM-6E special course.