Technological developments have significantly impacted various aspects of life, most notably healthcare and education. A nursing education shift was required to prepare digital generation. Consequently, nurse educators must adopt innovative approaches to teaching and learning, like incorporating immersive virtual reality (VR) into human anatomy courses to improve students' learning. To examine the influence of immersive VR applications (human anatomy) on self-directed learning (SDL) competencies among undergraduate nursing students. A cross-sectional design was conducted in the health profession's faculty at Al-Quds University among the first year of the nursing program, who were enrolled in an anatomy course (N = 137). The Self-Directed Learning Instrument was used, and independent sample t-tests were conducted to compare the level of SDL among students who utilized the VR application (Human Anatomy VR). The results showed that 93.9% of the total were approximately 20 years old, and 85.4% were females. 90.5% of participants expressed satisfaction with using the VR application and that it would be beneficial in nursing courses. The average score of SDL for the whole group was 72.03 ± 13.07, and there is a positive significant relationship between SDL and students utilizing VR (p < 0.001), between SDL competencies and technological skills (p = 0.009), and type of digital tools (p = 0.049). The highest coefficient of correlation was related to planning and self-monitoring (r = 0.918), and the lowest was related to interpersonal communications (r = 0.865). VR is an additional tool for enhancing learning, and nursing students perceive immersive VR technologies positively and prefer using three-dimensional images in their anatomy courses. SDL assists students in identifying learning objectives, barriers, and outcomes through using VR technologies as teaching strategies.