University electronic learning (e-learning) has witnessed phenomenal growth, especially in 2020, due to the COVID-19 pandemic. This type of education is significant because it ensures that all students receive the required learning. The statistical evaluations are limited in providing good predictions of the university’s e-learning quality. That is forcing many universities to go to online and blended learning environments. This paper presents an approach of statistical analysis to identify the most common factors that affect the students’ performance and then use artificial neural networks (ANNs) to predict students’ performance within the blended learning environment of Saudi Electronic University (SEU). Accordingly, this study generated a dataset from SEU’s Blackboard learning management system. The proposed model’s performance was evaluated through different statistical tests, such as error functions, statistical hypothesis tests, and ANOVA tests. The student’s performance can be tested using a set of factors: the studying (face-to-face or virtual), percentage of attending live lectures, midterm exam scores, and percentage of solved assessments. The results showed that the four factors are responsible for academic performance. After that, we proposed a new ANN model to predict the students’ performance depending on the four factors. Firefly Algorithm (FFA) was used for training the ANNs.