Many research problems in social science involve multilevel phenomena. However, discussions about multilevel research designs are limited in the mixed methods (MM) literature. Building on early writings in the field, this methodological discussion advances a refined definition of a multilevel MM research design. The refinement emerges from a review of qualitative and quantitative conceptions of multilevel research designs and an analysis of a literature-based definition of a multilevel MM research design. To illustrate the application of the refined definition, we present an exemplar of a multilevel MM study aimed at explaining cultural, behavioral, and neurobiological aspects of literacy for mathematics. This comprehensive and versatile definition advances the field by offering guidance for designing and conducting innovative multilevel MM studies.