Background: Hemodialysis patients deal with some psychological and social problems. These problems may be the predictors of hope. This study aimed to determine the psychosocial, spiritual, and biomedical predictors of hope in hemodialysis patients. Methods: This cross-sectional study was conducted on 350 hemodialysis patients in hemodialysis centers affiliated to Shiraz University of Medical Sciences. Adult Hope Scale, Depression Anxiety Stress Scales, Personal Resources Questionnaire-85, Spiritual Well-Being Scale, and biomedical markers were used for data collection. The data were entered into the SPSS 22 software and were analyzed using Pearson's correlation coefficient and linear regression analysis. Results: The mean score of hope was 28.54 (SD=5.27). The mean scores of depression, anxiety, and stress were 17.87 (SD=7.62), 13.12 (SD=3.47), and 12.99 (SD=3.88), respectively. The mean scores of social support and spiritual well-being were 126.35 (SD=17.53) and 74.02 (SD=5.84), respectively. The means of biomedical markers including interdialytic weight gain, urea nitrogen, creatinine, phosphate, sodium, and potassium were 2.10 (SD=1.04), 51.55 (SD=13.10), 6.98 (SD=2.48), 4.71 (SD=1.08), 139.32 (SD=4.91), and 4.87 (SD=0.93), respectively. The results revealed a significant association between hope and depression, anxiety, stress, social support, and spiritual well-being (p<0.05). In addition, stress (β=−0.14, p=0.01), anxiety (β=−0.20, p=0.002), and social support (β=0.49, p<0.001) were the predictors of hope. Conclusion: The hemodialysis patients reported moderate levels of hope, social support, anxiety, and depression. In addition, most of them adhered to dietary and fluid restrictions. Considering the association between hope and social support, spiritual well-being, anxiety, depression, and stress, using some interventions regarding the mentioned variables might increase hope among hemodialysis patients.