Background: Pregnant women, neonates, children, and adolescents are at higher risk of dying in fragile and conflict-affected settings. Strengthening the healthcare system is a key strategy for the implementation of effective policies and ultimately the improvement of health outcomes. South Sudan is a fragile country that faces challenges in implementing its reproductive, maternal, neonatal, child, and adolescent health (RMNCAH) policies. In this paper, we map the key RMNCAH policies and describe the current status of the WHO health system building blocks that impede the implementation of RMNCAH policies in South Sudan. Methods: We conducted a scoping review (39 documents) and individual interviews (n = 8) with staff from the national Ministry of Health (MoH) and implementing partners. We organized a workshop to discuss and validate the findings with the MoH and implementing partner staff. We synthesized and analyzed the data according to the WHO health system building blocks. Results: The significant number of policies and healthcare strategic plans focused on pregnant women, neonates, children, and adolescents evidence the political will of the MoH to improve the health of members of these categories of the population. The gap in the implementation of policies is mainly due to the weaknesses identified in different health system building blocks. A critical shortage of human resources across the blocks and levels of the health system, a lack of medicines and supplies, and low national funding are the main identified bottlenecks. The upstream factors explaining these bottlenecks are the 2012 suspension of oil production, ongoing conflict, weak governance, a lack of accountability, and a low human resource capacity. The combined effects of all these factors have led to poor-quality provision and thus a low use of RMNCAH services. Conclusion: The implementation of RMNCAH policies should be accomplished through innovative and challenging approaches to building the capacities of the MoH, establishing governance and accountability mechanisms, and increasing the health budget of the national government.