Priority setting and health system governance are critical for optimising healthcare interventions and determining how best to allocate limited resources. The COVID-19 pandemic has buttressed the need for these especially now that vaccines are available to curb the spread of the disease. In many low- and middle-income countries (LMICs), vaccine coverage remains low, due in large part to sub-optimal priority setting and health system governance which has led to inequities in access and has fuelled vaccine hesitancy. An analysis of the situation in Nigeria identified key issues that have affected the health system response to COVID-19 and impeded timely access to the vaccine. These include weak vaccine procurement strategies, limited evidence on strategies for prioritising recipients and approaches for rolling out mass vaccination programmes for the entire population, lack of a communication strategy to reduce the incidence of vaccine hesitancy and failures to proactively address vaccine hesitancy through the implementation of vaccination programmes. Nigeria and other many other LMICs are still facing the prospect of subsequent and potentially worsening waves of the COVID-19 pandemic. Without effective priority setting, there is a risk that the country will not accelerate vaccine rollout quickly enough to achieve high coverage rates that will ensure herd immunity. In the context of existing weaknesses in health system governance, there is an urgent need to strengthen priority settings in Nigeria and identify and implement context-specific solutions that can improve vaccine coverage for the population.