Nursing educators have the responsibility to equip nursing students with knowledge about the meaning of life, positive beliefs, and well-being in order to enhance their physical, psychological, spiritual, and social health education and promotion. The purpose of this study was to explore nursing students' simulated directed-learning in a life-education intervention on the meaning of life, positive beliefs, and well-being in regard to immediate and delayed effects in improving physical, psychological, spiritual, and social health education and promotion.The method of this study was constituted a quasi-experimental design with experimental and control groups for pre-test, post-test, and post-post-test. Purposive sampling and non-random distribution were used in the study. Assigned to the experimental group, 54 participants were third-year nursing students enrolled in a health education course with simulated directed-learning in a life-education intervention. Assigned to the control group, 56 participants were third-year nursing students enrolled in a caring care course without simulated directed-learning in a life-education intervention. A 56-item questionnaire was utilized, and the content validity index (CVI) was 0.95, as determined by seven expert scholars. The reliability of the questionnaire (n = 45) on Cronbach's α were: meaning of life 0.96, positive beliefs 0.95, and well-being 0.96. The statistical package SPSS 23.0 was used to analyze all of the data in the study. Frequencies, percentages, pre-test mean and SD, post-test mean and SD, post-post-test mean and SD, chi-squared test, t test, and generalized estimating equation (GEE) were employed for data analysis.Nursing students in the experimental group compared with the control group exhibited significant differences in meaning of life on the pre-post-test (β = 16.40, P < .001) and pre-post post-test (β = 25.94, P < .001), positive beliefs on the pre-post-test (β = 5.64, P < .01) and pre-post post-test (β = 9.21, P < .001), and well-being on the pre-post-test (β = 14.33, P < .001) and pre-post post-test (β = 23.68, P < .001).Nursing students in the experimental group showed a significant improvement in the simulated directed-learning with a life-education intervention on meaning of life, positive beliefs, and well-being in the immediate and delayed effects that enhanced their physical, psychological, spiritual, and social health education and promotion.