At a time when the world has suffered such an unprecedented event as the COVID-19 pandemic, it is essential to conduct research to evaluate the relationship of student satisfaction with interaction, Internet self-efficacy, and self-regulated learning in a fully online learning environment. The results of a survey of 290 students at a university in Viet Nam, using partial least squares structural equation modelling (PLS-SEM), indicate that four types of interaction (learner–learner interaction, learner–instructor interaction, learner–content interaction, and learner–technology interaction) positively and significantly affected students’ satisfaction with online learning, whereas Internet self-efficacy and self-regulated learning were not found to be significant predictors. These findings are crucial for enhancing the quality of online learning, which is regarded as not only the best cure for the massive global crisis COVID-19 has caused in education but also an innovative advancement compared with traditional face-to-face education. The authors discuss practical implications for instructional and course design, as well as directions for future research.