This study aims to explore the impact of teachers' transformative teaching practices on college students' mastery of 21st-century skills, with a focus on the teaching dimensions of "Personalized Considerations" and "Inspiring People," as well as the students' mastery of "Professional Skills" and "Life Skills." By analyzing students' assessments of their proficiency in 21st-century skills, the research demonstrates a significant positive correlation between transformative teaching behaviors and students' skill mastery. Specifically, the ability of teachers to motivate and provide personalized support significantly enhances students’ performance in learning, life, literacy, and professional domains. The data analysis revealed that students generally rated their mastery of 21st-century skills, including learning, life, literacy, and professional skills, as "agree," indicating a moderate level of manifestation. Additionally, differences in students' skill levels across gender, age, and grade level were found to be insignificant. However, the impact of transformative teaching practices on students' skill development was notably significant, particularly in the areas of "Charm Influence" and "Intellectual Stimulation." Regression analysis further highlighted that "Personalized Considerations" and "Inspiring People" teaching styles are strongly associated with students' mastery of 21st-century skills, especially in enhancing "Life Skills" and "Professional Skills." The proposed intervention program, developed from this study, aims to strengthen teachers' transformative teaching abilities to improve students' mastery of professional and life skills. Through personalized support and motivational guidance, college students will be better equipped to face future challenges in both their personal and professional lives. This study provides practical recommendations for educators to enhance teaching strategies to more effectively cultivate students' core 21st-century skills.