This study proposed a new conceptualization of technological pedagogical content knowledge (TPACK) that focuses exclusively on the intersection of technology, pedagogy, and content specifically for selected dimensions of 21st century learning. In addition, teachers' design beliefs were investigated with the teachers' TPACK. Given the conceptualization, a new instrument was designed and validated. An associated intervention program to enhance the preservice teachers' TPACK was designed and the pre- and post-course surveys were conducted. To unpack the relationships between teachers' design beliefs and their TPACK, structural equation models were constructed and validated. The findings indicate that the instrument possesses good construct, discriminant and convergence validity, and reliabilities. The intervention enhanced the teachers' TPACK efficacies and their design beliefs significantly, and the structural equation models indicate that the teachers' design beliefs are significant predictors of the teachers' TPACK. The implications of this study suggest that TPACK may be conceived differently and this may promote new intervention programs to foster preservice teachers' TPACK and design beliefs.