BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is rare and heterogeneous. Currently, there is no concise treatment standard for MANEC. This study aimed to explore the prognostic impact of different treatment methods in MANEC. METHODS: The surveillance, epidemiology and end results database was utilized to evaluate the outcomes of MANEC using propensity score matching (PSM) , stratified and site-specific survival analysis. RESULTS: A total of 935 patients diagnosed with MANEC were enrolled in this study. Across most analyses, surgery performance (compared with no surgery) was associated with improved survival outcomes for MANEC patients, except for the site-specific analysis of small intestine, in which no significant association between surgery and patients' survival was found. Radiotherapy exhibited no significant association with patients' survival in most cases, and associated with poor prognosis of MANEC in certain specific analyses. Inconsistent effects of chemotherapy on MANEC were observed. Positive impact of chemotherapy on MANEC was indicated in PSM for chemotherapy or radiotherapy. Contradictory effects of chemotherapy were suggested based on the stage of MANEC, with unfavorable outcomes in early-stage and favorable outcomes in advanced-stage. The impact of chemotherapy on survival was influenced by the administration of surgery or radiotherapy. Site-specific analyses indicated that chemotherapy was beneficial to MANEC of the hepatic-biliary-pancreatic system. CONCLUSIONS: The results of this study demonstrate the variable impact of different treatment strategies for MANEC. Surgery was generally associated with improved survival outcomes, while radiotherapy did not show a beneficial effect on MANEC. The effects of chemotherapy on MANEC were inconsistent in specific analyses.