The suffering experienced by terminally-ill patients encompasses physiological, psychosocial and spiritual dimensions. While previous studies have investigated symptom burden intensity for specific disease groups, such as cancer or heart failure patients, a research gap exists in understanding major distressing symptoms among diverse terminally-ill patients. This study assessed symptom burden intensity and explored its influential factors among diverse patient disease groups. This cross-sectional study utilized the baseline Integrated Palliative care Outcome Scale (IPOS) assessment data. The study participants were terminally-ill patients enrolled in an end-of-life care (EoLC) intervention in Hong Kong. Statistical methods including relative importance index (RII), one-way analysis of variance (ANOVA), and generalized linear regression (GLR) were employed. Final sample consisted of 1,549 terminally-ill patients (mean age =77.4 years, SD =11.6). The five top-rated distressing symptoms among these patients, revealed by the RII analysis, were poor mobility (RII =64.4%), family anxiety (RII =63.5%), sharing feelings with family/friends (RII =61.4%), weakness/ lack of energy (RII =58.1%), and hardly feeling at peace (RII =50.7%). One-way ANOVA showed significant differences among the eight disease groups in perceived physical and emotional symptom burden intensity (P<0.05). Analysis of RII symptom scores for each disease group revealed that poor mobility was rated as the most distressing symptom (RII =85.1-62.9%) by patients with motor neurone disease, Parkinson's disease, heart failure, dementia, end-stage renal disease and other serious diseases (including stroke, hematological disease, multiple sclerosis and liver diseases). Perceived family anxiety (RII =66.1%) and shortness of breath (RII =63.8%) were the most distressing symptoms for cancer patients and those with chronic obstructive pulmonary disease, respectively. GLR analysis showed that illness type is the most significant factor influencing the perceived burden intensity in terms of the IPOS total and subscale scores of physical symptoms, emotional symptoms and communication/practical issues. Demographic characteristics such as age, gender, marital status and co-residing status were also identified as influential factors of various symptom categories. However, patients' educational level and relationship with primary caregiver did not significantly influence any perceived symptom burden. This study provides valuable insights into the symptom burdens experienced by diverse patient disease groups at end-stage of life. The findings highlight the major distressing symptoms of poor mobility, family anxiety, and shortness of breath. Addressing these symptoms is crucial in improving the quality of care for terminally-ill patients. Furthermore, the study identifies influential factors that can affect the perceived intensity of symptom burden, primarily the main type of terminal illness and patient's age. Tailored care support and improved clinical care should be implemented, particularly for high-risk groups such as patients with non-cancer terminal illnesses and older aged patients. These findings contribute to existing literature and emphasize the need for comprehensive and individualized care in EoLC.