This chapter advocates a complex adaptive system of systems approach to understanding population-level processes in population health. A complex adaptive system consists of diverse, interacting adaptive entities whose aggregated behaviors result in emergent, system-level patterns and functionalities. A complex adaptive system of systems consists of multiple, connected complex systems. The connections can be hierarchical, horizontal, or a mixture of the two. The authors provide basic definitions, describe common tools of analysis, and introduce illustrative cases. For example, increased obesity levels have no single cause, nor do they arise from a single system. Instead, they arise from the interactions of multiple systems that operate at various levels of scale. Genetics and epigenetics play roles, as do nutrition, general health, advertising, infrastructure, social norms, exercise levels, and, as recent evidence suggests, the ecology of colonies of gut bacteria. Each of these contributors can be modeled as a complex adaptive system and the whole as a system of systems. Similarly, population-level disease outbreaks can be decomposed into separate systems, each with unique dynamics.