Mathematics teacher education in South Africa faces unique challenges shaped by the country’s social, cultural, linguistic, and economic diversity. Preparing teachers who can effectively engage with learners across such varied contexts requires a research agenda that foregrounds the mathematical work of teaching (MWT)—the specialized content knowledge, pedagogical reasoning, and classroom practices that enable effective mathematics instruction. This paper outlines a research agenda that emphasizes three key areas: (1) understanding how teachers engage with mathematical concepts and learners’ reasoning in multilingual and resource-constrained environments, (2) exploring the relationship between teachers’ professional knowledge and their instructional practices, and (3) examining the institutional and policy frameworks that shape teacher preparation and continuing professional development. The agenda calls for empirical studies, context-sensitive methodologies, and collaborative approaches that integrate teacher educators, researchers, and practitioners. By situating the mathematical work of teaching within South Africa’s diverse educational contexts, this research agenda seeks to inform policies and practices that strengthen teacher education, improve mathematics learning outcomes, and contribute to equity and quality in education.