Background: Patients with cancer often face some level of distress, regardless of disease stage. Distress in cancer survivors has a negative impact on their quality of life. The goal of this study was to identify risk factors for distress, understand how treatment associated with distress and reveal the relationship between the psychological and financial distress. Methods: This was a multi-center cross-sectional study of patients with cancer requiring surgery or chemotherapy. Patients completed questionnaires regarding their demographics, disease characteristics, psychological distress, and financial toxicity. A multivariable logistic regression model was used to examine factors associated with distress in surgical versus chemotherapy treatment groups.Results: A total of 409 patients participated in the study. Patients treated with surgery (n = 172) were more likely to be female, unemployed, early stage compared with patients undergoing chemotherapy (n = 237). Multivariable analysis revealed that surgical patients tended to have a higher risk of distress compared with patients receiving chemotherapy (OR, 95% CI: 3.086, 1.854–5.137) due to higher rates of nervousness, pain, and difficulty with bathing/dressing, and patients with high financial toxicity had a higher risk of distress compared with those with low financial toxicity (OR, 95% CI: 2.000, 1.278–3.130). The relationship between financial toxicity and psychological distress was stronger in the chemotherapy group, with the correction coefficient -0.294 and slope -1.196. Conclusion: Patients who underwent surgery and reported higher financial toxicity were more likely to experience distress. Multidimensional distress screening and psychosocial interventions should be provided pre- and post-operatively for patients.