To explore the potential profiles of the sense of coherence (SOC) among cancer radiotherapy patients using latent profile analysis (LPA) and to characterize each category. Additionally, we investigated the correlation between different profiles of the SOC and the coping strategies. Convenience sampling method was used to select 241 cancer radiotherapy patients hospitalized in a specialized hospital in Shanghai from March 2023 to October 2023 as research subjects. The study utilized a general information questionnaire, the Sense of Coherence Scale-13 (SOC-13), and the Medical Coping Modes Questionnaire (MCMQ) for the survey. LPA identified three potential profiles based on varying levels of SOC: "Low level-High meaningfulness" group (n = 38, 15.8%), "Moderate level-High manageability" group (n = 104, 43.2%), and "High level-Balanced" group (n = 99, 41%). Age (OR = 6.544, P = 0.015), residence (OR = 0.217, P = 0.004), initial recurrence (OR = 2.869, P = 0.028), and side effects (OR = 2.862, P = 0.015) were significant predictors. A lower level of the SOC was significantly associated with higher scores in acceptance-resignation (P < 0.001). The SOC among cancer radiotherapy patients can be divided into three potential profiles. Younger patients with side effect have lower levels of the SOC. Adopting a acceptance-resignation coping strategies is related to a lower SOC, suggesting that enhancing the level of the SOC plays a positive role in helping patients cope with stressful events.