The rapid development of technology has led to the emergence of innovative teaching approaches, such as high-fidelity patient simulation (HFPS). HFPSs have been shown to significantly enhance students' decision-making and intellectual skills. This study aimed to investigate how students learn from the pre-briefing to observation period of the facilitation of the HFPS based on the original quasi-experimental studies. This study analyzed the narratives from 92 students in the intervention group about their learning during the pre-briefing and observation of facilitation. The results indicated that the students learned more independently, received better support and resources for learning, were provided with more appropriate and safe care for the simulated case, and developed higher-level intellectual skills, such as self-directed learning, critical thinking, and clinical reasoning. Importantly, the structured guidelines provided roles and responsibilities and guiding questions or aspects for observation that directed the students to learn more actively and effectively while performing their roles in the HFPS. The structured guidelines serve as a roadmap to instruct students on learning during pre-briefing and applying what they have learned during the facilitation of the HFPS. This roadmap includes the learning journey from novice to competence in knowledge and skills and also from knowing to application. Therefore, this study's results have contributed important knowledge about well-structured HFPS guidelines for all stages of the HFPS, addressing the need for adequate guidance and learning support during the pre-briefing and observation of facilitation. The elements identified during the pre-briefing and observation of facilitation are crucial for directing students to learn and significantly enhance their understanding and application of knowledge and skills, ultimately promoting the development of higher-level intellectual skills, professionalism, and engagement. Nurse educators can incorporate these elements into HFPS training in curricula to enhance students' involvement and optimize the HFPS as an effective teaching tool with structured guidelines providing guidance and support throughout various stages of HFPS training.