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Introduction: In March 2014, the New South Wales (NSW) Government (Australia) announced the NSW Integrated Care Strategy. In response, a family-centred, population-based, integrated care initiative for vulnerable families and their children in Sydney, Australia was developed. The initiative was called 'Healthy Homes and Neighbourhoods'. A realist translational social epidemiology programme of research and collaborative design is at the foundation of its evaluation. Theory and Method: The UK Medical Research Council (MRC) Framework for evaluating complex health interventions was adapted. This has four components, namely 1) development, 2) feasibility/piloting, 3) evaluation and 4) implementation. We adapted the Framework to include: critical realist, theory driven, and continuous improvement approaches. The modified Framework underpins this research and evaluation protocol for 'Healthy Homes and Neighbourhoods'. Discussion: The NSW Health Monitoring and Evaluation Framework did not make provisions for assessment of the programme layers of context, or the effect of programme mechanism at each level. We therefore developed a multilevel approach that uses mixed-method research to examine not only outcomes, but also 'what is working for whom and why'.