This study investigated the conditions for developing science teachers’ Technological Pedagogical Content Knowledge (TPACK). It also explored the opportunities offered by two strategies to enhance science teachers’ ability to design technology-based inquiry activities for science learning: Experiencing Inquiry Model (EIM) and Metacognitive Scaffolding (MS). These strategies were adopted to support the processing necessary for developing teachers’ knowledge and for negotiating the integration of computer technology in science instruction. Situated Cognition Theory was used as a theoretical framework for learning, and TPACK was used as a conceptual framework for technology integration. 33 science teachers from four intermediate and high schools participated in the study. 17 and 16 teachers were conveniently assigned to EIM and MS, respectively. The study employed a mixed method of quantitative and qualitative evidence. As per the quantitative method, a quasi-experimental design that employed the 2 Teaching Strategy (EIM or MS) × 2 Time (pre- and post-intervention) of learning split-plot factorial design was applied in the study. Concurrently with the quantitative data collection, the qualitative evidence was collected from the researcher’s logbook, participants’ written documents, and interviews. The findings suggested that there were no significant differences between EIM and MS for developing the knowledge components embodied in TPACK. Nevertheless, the participants who learned through the MS strategy outperformed their counterparts in designing technology-based inquiry activities for science learning. The latter result suggested that teachers who received metacognitive scaffolding were more equipped to connect curriculum goals with technology and instruction.