The low motivation of students to learn science has been a concern for many science educators. This study determined the combined significant influence of perceived teacher professional development and 21st-century skills on students motivation in science. This study employed a quantitative design using descriptive-predictive approach involving 150 samples using a survey questionnaire. This study found that perceived teacher professional development and 21st-century skills among Grade 11 students were very high. Moreover, students motivation in science was high. Furthermore, there is a combined significant influence of perceived teacher professional development and 21st-century skills on students motivation in science. However, this conclusion does not fully support the self-determination theory since only one independent variable is found to be correlated with the dependent variable. This study recommends that teachers should help students connect science with other subjects and real-world scenarios. By incorporating interdisciplinary projects and inquiry-based learning experiences, students can become more engaged and find the learning process more relevant.