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This Commentary describes recent research progress and professional developments in the study of scientific teamwork, an area of inquiry termed the “science of team science” (SciTS, pronounced “sahyts”). It proposes a systems perspective that incorporates a mixed-methods approach to SciTS that is commensurate with the conceptual, methodological, and translational complexities addressed within the SciTS field. The theoretically grounded and practically useful framework is intended to integrate existing and future lines of SciTS research to facilitate the field’s evolution as it addresses key challenges spanning macro, meso, and micro levels of analysis.