Team science, defined as collaborative research efforts that leverage the expertise of diverse disciplines, is recognised as a critical means to address complex healthcare challenges, but the practical implementation of team science can be difficult. Our objective is to describe the barriers, solutions and lessons learned from our team science experience as applied to the complex and growing challenge of multiple chronic conditions (MCC). MCC is the presence of two or more chronic conditions that have a collective adverse effect on health status, function or quality of life, and that require complex healthcare management, decision-making or coordination. Due to the increasing impact on the United States society, MCC research has been identified as a high priority research area by multiple federal agencies. In response to this need, two national research entities, the Healthcare Systems Research Network (HCSRN) and the Claude D. Pepper Older Americans Independence Centers (OAIC), formed the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative to build nationwide capacity for MCC team science. This article describes the structure, lessons learned and initial outcomes of the AGING Initiative. We call for funding mechanisms to sustain infrastructures that have demonstrated success in fostering team science and innovation in translating findings to policy change necessary to solve complex problems in healthcare.