Contemporary science education requires teachers to facilitate learning that addresses complex, real-world problems beyond disciplinary boundaries. Yet, many in-service science teachers lack professional development that supports transdisciplinary problem-solving and innovative pedagogy. This qualitative study used a grounded theory (GT) approach to examine teachers’ experiences in a transdisciplinary, design-based training program and to develop a framework for effective professional learning. Participants engaged in sustained training grounded in design thinking and authentic problem contexts. Data were collected through semi-structured interviews, focus groups, reflective journals, training artifacts, and observations, and analyzed using constant comparative methods. Findings indicated shifts in teachers’ conceptions of problem-solving, enhanced capacity to integrate disciplinary and non-disciplinary perspectives, and changes in instructional planning and classroom practice. Design thinking functioned as a mediating process that helped teachers navigate ambiguity, collaboration, and iterative reflection. The resulting transdisciplinary design-based in-service science teacher training framework highlights key principles: authentic problem contexts, structured yet flexible design processes, collaborative inquiry, and iterative reflection. The study offers an empirically grounded framework with implications for teacher professional development, curriculum design, and policy.