Professional development programs might affect teachers' perceptions of how STEM disciplines are interconnected. The purpose of this research was to examine the change in perceptions of science teachers particularly in disadvantageous schools, who participated in a practice-based professional development program offered in Turkey, about STEM, entrepreneurship, and E-STEM, and their experiences related to E-STEM. This qualitative research had a phenomenological design. The participants were totally 30 science teachers who were teaching in each of the seven geographical regions of Turkey. The data were collected through semi-structured pre- and post-focus group interview forms finalized after the expert review and pilot study. Furthermore, the science teachers were asked to keep a diary about the implementation process throughout the research. The data collected through focus group interviews were examined using content analysis and the data collected through the diaries were examined using descriptive analysis. The findings of the study indicate that the science teachers defined E-STEM as a process containing the aspects of entrepreneurship (communication, perseverance and determination, self-confidence, motivation, risk-taking, presentation, and marketing) more comprehensively compared to the pre-interviews.