Due to the challenging nature of teaching and learning in the 21st century, educators must assume additional roles in schools to meet the expectations of students, parents, and communities. Studies in general have focused on all teachers as a group. The PISA 2015 assessment and analysis framework indicates that the focus of the current round of assessment is on science literacy. Therefore, science teacher professional collaboration, teaching self-efficacy, and teacher job satisfaction were also the focus of its measurement. In this study, 1039 science teachers from Hong Kong participated. Through literature review analysis, this study concluded that (a) teacher professional collaboration and teaching self-efficacy have a positive effect on job satisfaction; (b) teacher professional collaboration has a positive effect on teaching self-efficacy, and (c) teaching self-efficacy has a mediating role in teacher professional collaboration and teacher job satisfaction. A mediation model was developed to test this hypothesis. Data were analyzed using structural equation modeling (SEM). The results of the study confirmed our hypothesis. In addition, we examined the applicability of the model using multi-group SEM mode, and the results demonstrated that the effect of professional collaboration on job satisfaction among science teachers in Hong Kong, China did not differ by gender.