This research utilizes a mixed-method approach, integrating quasi-experimental design and quantitative triangulation methods to determine the impact of Case-Based Learning (CBL) and CBL supported by Concept Maps (CMs) on the theoretical knowledge comprehension abilities and metacognitive skills of medical students. In the first phase of the two-stage evaluation process, researchers administered a pre-test/post-test achievement test focusing on students' comprehension levels of theoretical knowledge; the data were analyzed using two-way ANOVA. The analysis results indicated a statistically significant increase in the average achievement scores across all learning environments; however, it was determined that this increase was not attributable to differences specific to the learning environments. In the second phase of the assessment, a new test was administered to not only assess the students' theoretical knowledge but also how they apply this knowledge in new and uncertain situations. The data obtained from this test, which targeted students' metacognitive skills and was administered after the experimental process, were analyzed using One-Way ANOVA to determine the effectiveness of the learning environments. The analysis results revealed that CBL significantly impacts metacognitive skills, and this effect is enhanced when supported by CMs. The findings demonstrate that CBL and CMs-supported educational approaches play a significant role in enhancing medical students' ability to effectively apply theoretical knowledge in the face of new and uncertain situations. These findings highlight the extensive utility of CBL and CM-supported approaches in enhancing critical metacognitive skills, essential for medical education. Furthermore, they suggest practical ways for integrating these methodologies into future curricula and refining educational strategies.