This study investigates teachers' perceptions about the presence of meaning, innovative behavior, burnout, openness toward organizational change, and principals' ethical leadership, focusing on their implications for 21st-century skills teaching. The research aims to determine if these factors individually or collectively influence teachers' readiness and capability to impart 21st-century skills in the class. Employing a quantitative, cross-sectional survey design, the study gathered data from 799 teachers who completed surveys in Şanlıurfa/Türkiye during the academic year 2022-2023. Results indicate significant relationships among all constructs in the study, from the presence of meaning to 21st-century skills teaching. Specifically, while teachers' perceptions of meaning and burnout are negatively correlated, innovative behavior, openness toward organizational change, and 21st-century skills teaching are positively correlated. The multiple regression analysis reveals that innovative behavior, openness toward organizational change, and perceived ethical leadership significantly predict 21st-century skills teaching while the presence of meaning and burnout do not contribute to the model significantly. Further explanations and suggestions are provided at the end of the paper.