<p>This study investigates the effectiveness of guided inquiry learning in enhancing scientific competencies among higher education students across diverse disciplines and demographic profiles. Using a quasi-experimental pretest–posttest design, the intervention was implemented in four undergraduate science courses—Physiology, Biophysics, Physics I, and Chemistry—offered by two faculties: Health Sciences and Polytechnic School. Initially, students engaged in traditional lecture-based learning before transitioning to guided inquiry activities supported by interactive PhET simulations tailored to course content. Scientific competencies were assessed before and after the intervention. Results revealed significant improvements across all courses (<i>p</i> &lt; .0001), with the greatest effect observed in Biophysics and the smallest in Chemistry. Gains were inversely related to baseline performance, indicating that students with lower prior knowledge benefited the most. When adjusted for baseline scores, Chemistry showed the highest relative gain, followed by Physiology, Biophysics, and Physics I. Gender differences were notable only in Chemistry, where female students outperformed male counterparts. Additionally, students in Health Sciences experienced greater overall improvement than those in Polytechnic courses. These findings highlight guided inquiry as a robust and inclusive pedagogical approach, particularly effective for learners with initially lower competencies. The variability in outcomes across disciplines and contexts underscores the need for adaptive instructional design that considers both subject matter and learner diversity. Overall, the study supports the integration of inquiry-based strategies as a means to foster active learning and scientific literacy in higher education settings.</p>