As many universities in non-Anglophone countries have committed to internationalising their academic programmes, more content courses in Arts and Sciences are being taught in English. When content courses are taught in English in a country where English is not the first language, this is called English Medium Instruction (EMI). Using specific country cases, previous studies have confirmed that an EMI course can pose many challenges to the learning of course content by students. To date, there have been few attempts to examine these challenges through a large-scale qualitative prism, which would be useful for gaining new insights in order to inform policy as well as classroom interventions. In this systematic thematic synthesis we have aimed to identify the obstacles to implementing learner-centred pedagogy in EMI tertiary programmes, focusing on student perspectives. The Critical Appraisal Skills Programme (CASP) and Consolidated Criteria for Reporting Qualitative Studies (COREQ) were used to appraise and synthesise 40 empirical articles. The articles included 1769 participants in 20 non-Anglophone countries and jurisdictions. The participants were both local and international non-native English-speaking students enrolled in EMI courses. The synthesis yielded 46 descriptive themes stratified into six analytical domains. The suggested domains are meta/linguistic, instructional, meta/cognitive, socio-cultural, affective, and institutional obstacles. They suggest that students in different regions faced quite similar challenges in their EMI courses. The challenges consist of inadequate use of English by students and lecturers, and a lack of student-centred pedagogy, particularly in teacher–student and student–student interactions. The findings of most learner-centred EMI studies revealed that the main challenges came from English comprehension (the first three suggested domains); fewer studies included factors related to the learning environment (the last three domains). This review can inform university administrators, teaching staff and researchers engaged in internationalising higher education and aid in designing appropriate EMI programmes that offer better learner-centred educational experiences.