The purpose of this study is to evaluate the impact of learner–content interaction, learner-learner interaction, learner–instructor interaction, self-regulated learning, and Internet self-efficacy is present on e-learning satisfaction. The gender effect is also included in the investigation of the impact. Many studies have been conducted to reveal learners’ satisfaction with e-learning, however, limited research has emphasized the gender effect in explaining learner satisfaction. A review of the existing literature was used to develop a conceptual model which was further tested using data collected from undergraduate students. The data collection used a self-administered questionnaire and 742 valid responses were acquired. Partial least square-structural equation modeling was used to analyze the model while multigroup analysis was used to assess the gender differences for the predictors. The results showed that learner–instructor interaction, learner-learner interaction, self-regulated learning, and Internet self-efficacy were predictors for learning satisfaction based on the overall sample. The university may use these factors as a reference to achieve learning satisfaction among students. Gender was found significantly different in the relationship between Internet self-efficacy and satisfaction. The finding suggests that the university administrators need to undertake strategic change to assist female learners in overcoming the barrier of Internet self-efficacy skills.