INTRODUCTION: In the Netherlands HPV-vaccination uptake is low among females with a Moroccan or Turkish migration background. The aim of this study was to identify health system barriers to HPV-vaccine uptake among these females. METHODS: A qualitative study, using semi-structured interviews and focus group discussions, was performed between October 2021 and June 2022. Included were female adolescents (12-18 years old), parents and grandparents who identify as 1st or 2nd generation migrants from Morocco or Turkey and healthcare professionals involved in childhood vaccinations working with the specific target populations. The World Health Organization (WHO) Health Systems Framework served as a conceptual model. RESULTS: Twenty-two community members and 12 healthcare professionals participated in the study. Health system barriers were found in four out of six building blocks. Reported barriers included a lack of awareness raising initiatives on HPV, lack of human resources available for tailored HPV vaccination, HCPs being insufficiently trained to provide tailored care, lack of or insufficient delivery of HPV (vaccination) information, language barriers, insufficient access to services, the lack of coordination between health services and providing the HPV vaccine as a stand-alone vaccine. CONCLUSION: Several health system barriers to HPV vaccination among female adolescents with a Moroccan or Turkish migration background in the Netherlands were identified. To increase HPV-vaccine uptake according to the WHO global strategies to eliminate the burden of cervical cancer, we need the development of tailored interventions that address these health system barriers and target these underserved populations.