While research has documented the key role of monitoring processes during hypermedia learning, limited empirical research has used process data to examine the possibility that these processes mediate the relationship between motivational constructs (such as self-efficacy) and cognitive factors (such as prior domain knowledge) with hypermedia learning outcomes. This multi-method study addressed this issue by examining: (1) The extent to which the relationship between self-efficacy and hypermedia learning outcomes is mediated by the use of specific monitoring processes and; (2) The extent to which the relationship between prior domain knowledge and hypermedia learning outcomes is mediated by the use of specific monitoring processes. Participants included 68 education majors. A self-report questionnaire was used to measure self-efficacy, a pretest was used to measure prior domain knowledge, a posttest was used to measure learning outcomes, and a think-aloud protocol were used to identify the deployment of monitoring processes during a 30-min hypermedia learning task. Results indicated that the relationship between self-efficacy and specific monitoring processes ("Monitoring Understanding", "Monitoring Environment", and "Monitoring Progress Towards Goals") was significantly detectable. Additionally, the relationship between prior domain knowledge and "Monitoring Understanding" was significantly detectable. Lastly, regression analyses revealed that the relationship between self-efficacy and hypermedia learning outcomes was mediated by the extent to which participants monitored their understanding and the environment.