As survival improves for individuals with cystic fibrosis (CF) worldwide, the number of adolescents requiring transition from pediatric to adult care is rapidly growing. In addition to limited resources, lack of uniform access to medical care, access to traditional and advanced therapies, the increasing number of transitioning young adults in low- and middle-income countries (LMICs) face barriers and challenges to safe transition from pediatric to adult healthcare that are both universal and unique. This shift in demographics presents distinct challenges due to underdeveloped and under-resourced adult CF care infrastructure, sociopolitical variation, and cultural complexities. This manuscript focuses on healthcare transition (HCT) of people with CF (pwCF) in LMICs, identifies key barriers, and explores cultural, religious, and health system factors. Additionally, we emphasize the practical need to transition adolescents to adult care to maintain pediatric hospital capacity for younger children, as well as the developmental and educational needs of young adults entering a medical system that is challenging for adults without chronic disease. With much of the transition literature reflecting health systems in high-income countries (HIC), this integrated socio-ecological and socio-cultural overview underscores the urgent need for context-specific, culturally sensitive transition frameworks focused on reproductive and mental health, the integration of adolescent-responsive, family-inclusive, and even faith-informed care models in LMICs.