Context: The Australian Nurse-Family Partnership Program is a home visiting program for Aboriginal mothers and infants (pregnancy to child's second birthday) adapted from the US Nurse Family Partnership program. It aims to improve outcomes for Australian Aboriginal mothers and babies, and disrupt intergenerational cycles of poor health and social and economic disadvantage. The aim of this study was to describe the complexity of Program clients in the Central Australian family partnership program, understand how client complexity affects program delivery and the implications for desirable program modification. Methods: Australian Nurse-Family Partnership Program data collected using standardised data forms by nurses during pregnancy home visits (n = 276 clients from 2009 to 2015) were used to describe client complexity and adversity in relation to demographic and economic characteristics, mental health and personal safety. Semi-structured interviews with 11 Australian Nurse-Family Partnership Program staff and key stakeholders explored in more depth the nature of client adversity and how this affected Program delivery. Findings: Most clients were described as “complicated” being exposed to extreme poverty (66% on welfare), living with insecure housing, many experiencing domestic violence (almost one third experiencing 2 + episodes of violence in 12 months). Sixty-six percent of clients had experienced four or more adversities. These adversities were found challenging for Program delivery. For example, housing conditions mean that around half of all ‘home visits’ could not be conducted in the home (held instead in staff cars or community locations) and together with exposure to violence undermined client capacity to translate program learnings into action. Crises with the basics of living regularly intruded into the delivery of program content, and low client literacy meant written hand-outs were unhelpful for many, requiring the development of pictorial-based program materials. Adversity increased the time needed to deliver program content. Conclusions: Modifications to the Australian Nurse-Family Partnership Program model to reflect the specific complexities and adversities faced by the client populations is important for effective service delivery and to maximise the chance of meeting program goals of improving the health and well-being of Australian Aboriginal mothers and their infants.