Background: Thalassemia is a hereditary blood disorder that poses significant challenges for affected children and their families. Caregivers, particularly mothers, often experience difficulties in managing their child’s condition. Understanding their current experience is crucial for improving care and support. Objective: This study aimed to explore the experiences of mothers caring for children with thalassemia in Banten, Indonesia. Methods: A qualitative descriptive approach was employed, involving semi-structured in-depth interviews with eleven mothers of children diagnosed with thalassemia. Data were collected from April to May 2023. The interviews were audio recorded, and the data were analyzed verbatim using Colaizzi’s method to identify key themes related to the experiences. Results: Three themes were developed: 1) Perception of thalassemia as a genetic condition, 2) Emotional, logistical, and practical caregiving challenges, and 3) Support received by mothers in caring for children with thalassemia. Conclusion: The findings highlight the multifaceted challenges faced by mothers of children with thalassemia and emphasize the need for improved communication, emotional support, and care coordination from nurses and healthcare providers. Future research should focus on expanding support systems and exploring effective interventions to enhance the quality of life for families navigating the complexities of chronic illness. © The Author(s) 2024.