Objective To describe the current status of transition preparation among adolescents with thalassemia major (TM), identify its influencing factors, and provide a basis for transition-period interventions. Methods A convenience sampling approach was used to recruit 138 adolescent inpatients with TM from two tertiary Grade A hospitals in western Guangxi from April to December 2024. Data were collected using a general information questionnaire, a transition preparation questionnaire, the Pediatric Quality of Life Inventory Generic Core Scales, and the Family Caregiving Measurement Scale. Multivariable regression analysis was conducted to determine factors associated with transition preparation. Results Among the 138 adolescents with TM, the mean total transition preparation score was 59±9, the family caregiving score was 189±23, and the quality of life score was 57±14. Age, disease duration, monthly family income, exposure to transition-related information, caregiver education level, family caregiving level, and quality of life level were significantly associated with transition preparation (P<0.05). Conclusions Transition preparation among adolescents with TM is at a moderate level. Nursing staff should tailor family-focused interventions according to patient age and family caregiving capacity to promote transition preparation and improve quality of life.