In an era of rapid digital development, e-learning has become a significant trend in the educational field. Medical technology students need to acquire extensive theoretical knowledge and practical skills. E-learning can enhance learning experiences, improving students’ understanding and application abilities. This study examined the impact of learning motivation, learning approaches, and learning burnout on the academic performance of medical technology students in an e-learning environment. This study conducted a quantitative survey on 37 medical technology students. The questionnaires included learning motivations, learning methods, and burnout, and responses provided on a 5-point Likert scale. First, the 37 students were categorized into three groups based on their academic performance. Then, differences between these groups were analyzed using the Kruskal-Wallis test, and correlations between academic performance and questionnaire variables were calculated using Spearman correlation analysis. It revealed that motivation varies among different academic performance levels. Furthermore, in the high-grade group, self-efficacy (r = -0.502, p = 0.047), monitoring studying (r = 0.494, p = 0.032), and emotional exhaustion (r = 0.514, p = 0.024) were correlated to academic performance. In the middle-grade group, self-efficacy for learning and performance was correlated to academic performance (r = 0.858, p = 0.001). In the low-grade group, academic performance was correlated to depth approach (r = 0.826, p = 0.022) and organized studying (r = 0.833, p = 0.020). This study, through a quantitative survey, found significant differences in learning motivation, learning methods, and learning burnout among medical technology students with different academic performance levels. High-grade students demonstrated higher levels of emotional exhaustion, which may reflect feelings of overextension and academic burnout in e-learning environments; the academic performance of the middle-grade group was related to intrinsic motivation; and low-grade students showed a stronger correlation between their learning methods in e-learning and their academic performance. These insights underscore the necessity for personalized learning strategies to enhance educational outcomes effectively.