(a) To identify subgroups with unique psychoneurological symptom-cluster experience (depression, cognitive impairment, fatigue, sleep disturbance, and pain) and (b) to examine whether the selected demographic, clinical, psychological, and biological factors determine a symptom-cluster experience in cancer patients.The sample included 203 patients with diverse cancer types recruited from a Korean university hospital. Latent profile analyses were conducted to identify subgroups. Influencing factors of subgroup membership (demographic/clinical variables, hemoglobin level, social support, and psychological stress) were included as covariates in latent profile analysis and analyzed by multinomial logistic regression.Latent profile analyses classified patients into two subgroups with a unique symptom cluster experience: patients experiencing high intensity in all symptoms within the cluster (the all-high-symptom subgroup, 71%) and patients experiencing low intensity in all symptoms within the cluster (all-low-symptom subgroup, 29%). The validity of the two subgroups was confirmed by the group classification accuracy (97% of the all-low-symptom subgroup and 99% of the all-high-symptom subgroup) and by significant Wald's mean equality tests, showing each symptom (depression, cognitive impairment, fatigue, sleep disturbance, and pain) significantly differentiated the two subgroups (ps < .001). Psychological stress independently determined the subgroup membership. Patients with high levels of stress were more likely to be in the all-high-symptom group (OR = 4.69, p < .0001). Hemoglobin level, cancer diagnosis, social support, and previous chemotherapy experience did not influence group membership.A large number of patients experience five psychoneurological symptoms simultaneously due to psychological stress. Interventions targeted to stress would be beneficial for those patients.