This study centers on designing a targeted professional development (TPD) model to enrich the Entrepreneurial-STEM (E-STEM) literacy of teachers within an integrative conceptual framework. The study is threefold in its purpose: firstly, to investigate the impact of a targeted E-STEM PD on teachers' pedagogical growth (PG), emphasizing familiarity, interest, and confidence in E-STEM literacy principles; secondly, to assess teachers' satisfaction with the TPD content and its delivery format; and thirdly, to explore their perceptions regarding the efficacy of this TPD in empowering them to implement E-STEM learning. A mixed-methods approach was employed through a quasi-experiment involving a single group of 220 teachers from different Communities of Practice (CoPs) across various educational stages. Results revealed a significant positive impact on enhancing the pedagogical principles of E-STEM literacy among teachers, indicating substantial improvements in their three PG components. Participants expressed high satisfaction with the E-SETM TPD content and various delivery formats, underscoring its effectiveness in meeting their needs. This research highlights the strategic importance of teacher professional learning in E-STEM, emphasizing its role in fostering innovation, research, and a skilled workforce.