The study aimed to assess the strengths and weaknesses, opportunities and threats influencing the achievement of prevention of mother-to-child transmission of hepatitis B virus. It also sought to suggest recommendations to improve the current prevention of mother-to-child transmission of hepatitis B virus health system in Nigeria. A critical appraisal of the prevention of mother-to-child transmission of hepatitis B virus health system in Nigeria was conducted. The WHO health system framework was used to assess the prevention of mother-to-child transmission of hepatitis B virus system. Considering the recent call by the World Health Organization to eliminate hepatitis and the existence of a robust prevention of mother-to-child transmission of human immunodeficiency virus health system, the prevention of mother-to-child transmission of hepatitis B virus health system in Nigeria is riddled with numerous challenges. These range from a health worker crisis, poor leadership and governance, inadequate health information, medicines, vaccines and technologies and poor service delivery. Urgent action in the Nigerian prevention of mother-to-child transmission of hepatitis B virus health system is required if Nigeria is to achieve its goal of eliminating hepatitis by 2021.