Purpose: This study aims to investigate the role of the Technological Pedagogical Content Knowledge (TPACK) framework in preparing pre-service teachers for effective teaching in digitally mediated classrooms. Research Methodology: This study employed a mixed-methods approach in which quantitative data were collected through a structured questionnaire measuring technology integration self-efficacy among 238 pre-service teachers from three universities in North Central Nigeria, while qualitative data were obtained from reflective journals and focus group discussions to explore participants’ experiences and understanding of technology integration in teaching and learning. Results: The findings show that TPACK-based coursework improves pre-service teachers’ confidence and understanding of integrating technology into teaching, especially through collaborative, reflective, and practical learning experiences. Conclusions: The study concludes that the systematic integration of TPACK within teacher education curricula is essential. Combining technological, pedagogical, and content knowledge can better prepare future teachers to effectively teach in increasingly digital learning environments. Limitations: The study is limited to three universities within one region (North Central Nigeria), which may restrict the generalizability of the findings. In addition, the data rely largely on self-reported measures, which may introduce subjective bias, and the study does not directly assess long-term classroom teaching practices. Contributions: This study provides empirical evidence on the effectiveness of the TPACK framework and emphasizes the importance of integrating technology, pedagogy, and content knowledge to enhance pre-service teachers’ digital competence.