Although there is an established body of work arguing that teachers' technological pedagogical content knowledge (TPACK) is necessary for designing ICT-integrated lessons, little is known about the relationships among teachers' beliefs about learning, their design dispositions, learning design practices and TPACK. Critical inquiry in this aspect is timely as a new culture of learning is emerging from the informal contexts of learning and challenging how school-based learning should be designed to foster 21st century competencies. In this study, a survey instrument was developed to assess and investigate the relationships among pre-service teachers' beliefs about the new culture of learning and school-based learning, their design dispositions, learning design practices and relevant factors of TPACK. Based on the sample size of 223 pre-service teachers in Singapore, the validation shows that the relevant factors pertaining to TPACK, teachers' beliefs and design were distinctive. The study shows that teachers' beliefs about learning and their design capacities changed along with their TPACK efficacy. It also identified factors that might affect teachers' competencies needed to design lessons that could cultivate a new 21st century culture of learning. Implications of the relationships among teachers' beliefs about learning, their design capacities and TPACK to foster 21st century competencies are discussed.