This study utilizes a comparative experimental research method to investigate the effect of the Predict, Observe, Explain, and Evaluate (POEE) learning strategy in an immersive virtual environment (IVE) on two types of learners with different levels of prior knowledge. One type referred to as Highly Experienced and Knowledgeable (HEK) learners, has both experience in using IVE and subject background knowledge, while the other type, referred to as Limited Experience or Knowledge (LEK) learners, lacks experience in using IVE or subject background knowledge. A total of 65 seventh-grade students from a middle school in Wuhan participated in the experiment, engaging in self-directed learning activities in the IVE. The research results indicate that the implementation of the POEE learning strategy enhances learner-content (L-C) interactions, leading to improved learning outcomes in self-directed learning in the IVE. These improvements are particularly evident in the following aspects: (1) improve LEK learners' academic performance and promote knowledge retention and transfer; (2) improve learners' cognitive, behavioral, and affective engagement; (3) increase learners' motivation and self-efficacy, and decrease their cognitive load. Findings from this study contribute to a better understanding the nature and diversity in student interactions and offer valuable insights for the design of self-directed learning in an IVE.