Introduction: In South Africa over the past 20 years, immunisation has saved countless lives as well as prevented illnesses and disabilities. Despite this, vaccine-preventable illnesses remain a danger. The demand for and uptake of immunisation services are shaped by a variety of factors that can either act as barriers or facilitators to immunisation uptake. The aim of this project was to identify the supply and demand barriers and develop local strategies to improve childhood immunisation in four zero-dose districts in South Africa. Materials and Methods: This study used a mixed-method approach. In each of these four districts, 15 in-depth key informant interviews with health workers and local health managers and four focus group discussions (10 participants per focus group discussion) with community members and caregivers were held over a three-month period. Transcribed interviews were thematically analysed using qualitative analysis software (Nvivo®) into 10 factors as identified as important in influencing immunisation demand and uptake in previous studies. A further four were identified during the data analysis process. Results: Despite the varying role of factors affecting demand and uptake of immunisation services, three consistent findings stand out as major barriers across all districts. The first is interaction with healthcare staff. This clearly highlights the crucial role that the interactions between patients and staff play in shaping perceptions and behaviours related to immunisation services. The second is the overall experience of care at healthcare facilities. This emphasises the role that patient experience of services plays in perceptions and behaviours related to immunisation services. The third is family dynamics. This highlights the important role family dynamics play in shaping individuals' decisions regarding immunisation uptake as well as the impact it has on the ability of people to access health services. Discussion: The role played by the different factors in the demand and uptake of immunisation services varied across the four districts examined in this study. Each of the districts presents a unique landscape where different factors have varying degrees of importance in affecting the utilisation of immunisation services. In some districts, certain factors are major barriers, clearly hindering the demand and uptake of immunisation services, while in others, these same factors might be a relatively minor barrier. This discrepancy highlights the unique nature of healthcare challenges across the districts and the need for tailored strategy recommendations to address them effectively.