In student-centric learning environments, such as blended learning, students' metacognitive self-regulation is required to plan, monitor, and control their learning processes and achieve positive learning outcomes. The lack of metacognitive self-regulation may lead students to encounter difficulties that, eventually, affect their learning perceptions. Therefore, understanding how to drive students' metacognitive self-regulation is essential to delivering an effective blended learning process that supports students' learning perceptions. This study examines the structural relationships between academic self-efficacy, student-student interaction, student-lecturer interaction, metacognitive self-regulation (including planning, monitoring, and regulating), and perceived learning using structural equation modeling. The data were collected from 1675 undergraduate students who experienced blended learning at Egyptian universities. The findings revealed that academic self-efficacy, student-student interaction, and student-lecturer interaction have significant direct effects on the planning, monitoring, and regulating dimensions of metacognitive self-regulation. Furthermore, metacognitive self-regulation dimensions not only influence perceived learning but also mediate the effects of academic self-efficacy, student-student interaction, and student-lecturer interaction on perceived learning, except for monitoring, which has an insignificant mediation effect on the relationship between student-student interaction and perceived learning. The findings of this study may help researchers, practitioners, and stakeholders gain deep insights regarding how to promote tertiary students' metacognitive self-regulation and learning perceptions during the blended learning experience.