Introducing innovative health interventions into clinic settings requires a comprehensive and creative approach to multiple implementation challenges. To optimize implementation of a sexual and reproductive health intervention for young women with depression, we applied systems thinking and human-centered design thinking methods to develop tools and strategies to address issues influencing intervention implementation in diverse clinics. We recruited staff from three clinics that provide sexual and reproductive health and behavioral health care to young women. Across five sessions (four video conference calls, one in-person workshop), we used systems mapping to identify key stakeholders and their relationships, processes, and challenges to care; formed clinic staff-investigator design teams; brainstormed about challenges that would influence intervention implementation and considered potential solutions; prioritized implementation challenges; and designed prototypes of solutions. Participants responded positively to the systems thinking perspective and collaborative design thinking process, which resulted in generalizable considerations about solving implementation challenges for clinic-based interventions.