In the context of the current teacher education program in Thailand, Technology Pedagogical and Content Knowledge (TPACK) framework is formally recognized as essential qualities of knowledge for a highly qualified preservice teacher in today's education. TPACK has been attracted to educational researchers for preparing preservice science teachers nationwide. In this study, TPACK was employed for restructuring a preservice science teacher education course with mobile game technology, which was offered in two consecutive semesters with a total enrollment of 115 student teachers in the first cohort and 94 student teachers in the second cohort. A pedagogic module of Mobile Game-based Inquiry Learning in Science (MGILS) has been designed and created in two settings, a usual separated and integrated case-based TPACK support module, and then implemented with the first and second cohort respectively in general science teacher education program at a Rajabhat University of Thailand. They were measured TPACK in terms of four constructs, namely, (a) technological knowledge (TK), (b) technological content knowledge (TCK), (c) technological pedagogical knowledge (TPK), and (d) technological pedagogical content knowledge (TPCK). Considering both qualitative and quantitative data analysis from two cohorts, the results showed preservice science teachers' incremental TPACK improvement from the implementation of the usual separated and integrated case-based TPACK support module of MGILS. Based on the results of MGILS intervention, it seems to indicate the alleged superiority of the integrated case-based TPACK support over the usual separated TPACK support. The deficits in the use of MGILS module are identified, and possible improvements to enhance TPACK in the mobile game are proposed.