Comfort in patients with coronary heart disease (CHD) is crucial to accelerate the healing process during their stay in intensive care units (ICUs). Factors contributing to patient comfort are essential in providing comprehensive nursing care. This study aims to investigate the relationship among variables, including patient characteristics, emotional response, healthcare service, Islamic spirituality, spiritual meaning, and comfort in patients with CHD. A cross-sectional study was conducted, involving 110 respondents in the ICUs of hospitals across Central Java Province, Indonesia, from January to May 2023. The sample was taken using purposive sampling. The data were collected using questionnaires that had been modified under a permission from the authors. SmartPLS 3 with partial least square structural equation modelling (PLS-SEM) was employed to analyze the correlation among the variables. The result showed that patient characteristics showed significant correlations with emotional response (t=2.082, p=0.038) and spiritual meaning (t=3.142, p=0.002). Similarly, support significantly correlated with emotional response (t=4.032, p<0.001) and spiritual meaning (t=2.448, p=0.015). Healthcare service exhibited significant correlations with emotional response (t=9.485, p<0.001) and spiritual meaning (t=5.249, p<0.001). Emotional response was found to correlate with Islamic spirituality and spiritual meaning (t>1.96, p<0.05), while Islamic spirituality showed a significant correlation with spiritual meaning (t=2.727, p=0.007). Finally, spiritual meaning significantly correlated with comfort (t=6.119, p<0.001). In conclusion, this study demonstrated significant correlations among variables such as patient characteristics, support, healthcare service, emotional response, Islamic spirituality and spiritual meaning to enhance patient comfort in ICUs. Policymakers should pay attention to factors affecting patient comfort during their stay in ICUs, including physical, psychospiritual, sociocultural, and environmental comfort based on self-regulation.