(1) Background: Sleep quality is one of the most important clinical outcomes of hemodialysis (HD) patients, as it can affect their physical and mental health. This study aimed to investigate sleep quality and its affecting factors among patients with HD. (2) Methods: A cross-sectional design was used to investigate the quality of sleep among HD patients in two cities in Saudi Arabia. The data were collected during the period from January to December 2022. A convenience sample of 250 HD patients was selected in this study. Data were collected using the Arabic version of the Pittsburgh Sleep Quality Index (PSQI). (3) Results: About two-thirds of participants (63.6%) had normal sleep, while one-third had poor sleep (36.4%). There was a significant relationship between the participants' age and the quality of sleep, where participants who were aged more than 50 had poorer sleep than those who were younger ( < 0.001). Male and married participants significantly had poor sleep more than female and single participants ( = 0.011 and 0.015, respectively). In addition, participants who were retired, had a higher number of dependents, did not adhere to exercise, and had more comorbidities had significantly poorer sleep than other groups ( = 0.002, 0.016, 0.023, and <0.001, respectively). The level of education, financial status, distance from home to dialysis center, and participants' satisfaction at the time of dialysis had no influence on the quality of sleep among HD patients. The multiple linear regression shows that exercise ( = 0.017), the number of comorbidities ( = 0.008), and the duration of dialysis ( < 0.020) were the independent factors affecting the quality of sleep among HD patients. (4) Conclusions: About one-third of HD patients in this study had poor sleep. There were significant differences between patients' age, gender, marital status, and sleep-quality levels. Moreover, participants who retired, had a higher number of dependents, did not adhere to exercise, and had more comorbidities had significantly poorer sleep than other groups. Future studies should develop appropriate interventions to address the problem of poor sleep quality among HD patients.