Sociocultural determinants affect the physical and mental well-being and coping of individuals with chronic illnesses. However, no studies have examined the relationship of sociocultural determinants with psychological distress and coping. The purpose of this study was to determine the levels of psychological distress and coping among individuals with chronic illness and identify sociocultural determinants affecting distress and coping. A cross-sectional design was used. Data were collected from a convenience sample of 384 individuals admitted to inpatient settings and attending outpatient clinics at two tertiary care hospitals. The validated Urdu-translated version of the Hospital Anxiety and Depression Scale, and the Brief COPE scales were used for data collection. The mean HADS-Depression score was (11.38 ± 2.53), and the HADS-Anxiety score was 13.42 ± 2.34), indicating high levels of depression and anxiety. The most commonly used coping strategies were problem-focused coping (15.95 ± 4.95), followed by emotion-focused coping (15.01 ± 2.33), and avoidance coping (13.89 ± 4.77). Higher levels of psychological distress in individuals with chronic illnesses underscore the importance of implementing community-based support approaches. Varied use of coping strategies was influenced by the type of chronic illness, living conditions, educational level, years of living with a chronic illness, family dynamics, and available support systems.