Esophageal cancer is one of the most prevalent malignancies. This study aimed to examine the impact of factors such as immunotherapy, altitude, radiotherapy target volume, and radiotherapy dose on the prognosis of patients with locally advanced and advanced esophageal cancer who are receiving definitive radiotherapy and living in high-altitude regions. We retrospectively collected data from all patients with locally advanced and advanced esophageal cancer who completed definitive radiotherapy at Yunnan Cancer Hospital between January 2017 and January 2023. A total of 274 patients were included, with a median follow-up time of 24.5 months. The median overall survival (OS) and progression-free survival (PFS) were 15.0 months and 11.0 months, respectively. Adjuvant therapy (including chemotherapy, immunotherapy, and antiangiogenic targeted therapy, P = 0.004) and gross target volume (GTV, P = 0.015) were independent predictors of overall survival, whereas body mass index (BMI, P = 0.037) was an independent predictor of progression-free survival. Patients with a smaller planning target volume (PTV), clinical target volume (CTV), GTV, and gross tumor volume of metastatic regional lymph nodes (GTVnd), as well as those with a smaller New target volume, had a better prognosis. Treatment efficacy affects patient prognosis, with those showing early therapeutic effectiveness having a better prognosis than those for whom the treatment is ineffective. Patients who experienced disease progression within three months after the end of radiotherapy had a poorer prognosis. The altitude and radiotherapy dose had no significant impact on the prognosis of esophageal cancer patients. The location of the lesion, GTV, and simultaneous integrated boost (SIB) radiotherapy were factors influencing the occurrence of esophageal fistulas.