Background Gender equity in academia is a significant challenge. To investigate career advancement perspectives of mid-career female physician-scientists, identify their needs and barriers, and develop a mentor-sponsorship strategy to improve their representation in higher academic ranks. Methods In this qualitative study, conducted at a Western European academic medical center, we interviewed 19 mid-career female physician-scientists across all specialties, including radiology. Data were analyzed using thematic analysis. Results Four themes were identified: 1. Horizontal and vertical ambitions, (i.e., knowledge expansion and hierarchical advancement) 2. Evaluation of talent, 3. Career path needs, and 4. Receiving support. These themes revealed barriers to women's advancement, including limited talent recognition, inadequate leadership support, self-limiting beliefs, structural issues, and lack of networking opportunities. To address these challenges, a mentor-sponsorship program should prioritize sponsor training, start immediately at the beginning of the mid-career phase (attainment of assistant professorship), emphasize horizontal and vertical development, take work-life balance into account, establish mentor networks, and allow individuals to choose mentors and sponsors based on their needs and aspirations. Conclusions This study has identified key needs and barriers that impede the advancement of female physician-scientists in academia. To address these challenges, a tailored mentor-sponsorship program is recommended. Key program elements include training leadership to recognize talent and offer proactive support, starting at the onset of the mid-career phase, emphasizing horizontal and vertical development, and establishing a strong mentor-sponsor network with thoughtful matching. These actions can help to overcome obstacles and facilitate the progress of women in academia.