Area-based strategies have been widely employed in efforts to improve population health and take action on social determinants of health (SDH) and health inequities, including in urban areas where many of the social, economic and environmental factors converge to influence health. Increasingly, these factors are recognized as being part of a complex system, where population health outcomes are shaped by multiple, interacting factors operating at different levels of social organization. This article reports on research to assess the extent to which an alliance of health and human service networks is able to promote action on SDH within an Australian urban region, using a complex systems frame. We found that such an alliance was able to promote some effective action which takes into account complex interactions between social factors affecting health, but also identified significant potential barriers to other forms of desired action identified by alliance members. We found that a complex systems lens was useful in assessing a collaborative intervention to address SDH within an urban region.