$Background:$ The early stages of a systematic review set the scope and expectations. This can be particularly challenging for complex interventions given their multidimensional and dynamic nature.

$Rationale:$ This paper builds on concepts introduced in paper 1 of this series. It describes the methodological, practical, and philosophical challenges and potential approaches for formulating the questions and scope of systematic reviews of complex interventions. Furthermore, it discusses the use of theory to help organize reviews of complex interventions.

$Discussion:$ Many interventions in medicine, public health, education, social services, behavioral health, and community programs are complex, and they may not fit neatly within the established paradigm for reviews of straightforward interventions. This paper provides conceptual and operational guidance for these early stages of scope formulation to assist authors of systematic reviews of complex interventions.