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This study investigated the clinical characteristics and symptomatology of ESRD patients in Jordan taking a multidimensional approach. This was a cross-sectional study that included a cohort of 620 patients undergoing maintenance hemodialysis (HD). Data were retrieved via patient survey administration and electronic health records. A modified version of the Charlson Comorbidity index (CCI) was utilized to assess comorbidity. Symptoms were assessed using the validated Arabic version of the CKD Symptom Burden Index (CKD-SBI). The mean (± SD) age of participants was 50.9 ± 16.1 years, with the 59.8% being males. Diabetes was the leading cause of kidney disease among patients (29.2%), followed by hypertension (20.7%) and medication use (8.6%). Common comorbidities included hypertension (72.4%), diabetes (38.4%), and cardiovascular disease (18.7%). Patients experienced 13 CKD-related symptoms on average, with a total symptom burden score of 29.6. Muscle strain was the most common symptom (62.6%), followed by itchiness (59.7%), nervousness (57.7%), and anxiety (57.7%). Charlson comorbidity index (CCI) [β = 0.88, 95% CI (0.34–1.41)], male gender [β = − 5.59; 95% CI (− 8.34 to − 2.85)], higher educational level [β = − 3.38; 95% CI (− 6.39 to − 0.37)], and number of dialysis sessions/week (β = 6.22, 95% CI 3.37–9.07) were independent predictors of total symptom burden. Similarly, these factors predicted symptom troublesomeness, intensity, and recurrence. A holistic clinical picture of ESRD that includes multidimensional symptom assessment is warranted for better disease management and resource allocation. Our paper identifies key characteristic of this population and factors contributing to total symptom burden.