Simple SummaryMesotheliomas arising from the lining of the mesothelial cells of the peritoneum are rare. However, they are strongly linked to asbestos exposure, similar to the relatively well-known pleural mesotheliomas. It is slightly more common in men than in women, with the majority of cases seen in Caucasians older than 50 years. Distant spread of tumor, size > 4 cm, and negative lymph node status were observed in our study among the patients with evaluable data. Optimal outcomes are achieved when patients are treated in specialized centers with surgical debulking followed by heated chemotherapy administered intraoperatively. Systemic chemotherapy and radiation are options for the selected patient groups. Patients with poorly differentiated large tumors (>4 cm), Caucasian race, and distant spread of disease outside the abdominal cavity have worse prognosis.Background: Primary peritoneal mesothelioma (PPM) is a rare and aggressive tumor arising from the visceral and parietal peritoneum. The diagnosis and treatment of PPM are often delayed because of non-specific clinical presentation, and the prognosis is worse. The current study investigated the demographic, clinical, and pathological factors affecting patient prognosis and survival in PPM. Methods: Demographic and clinical data of 1998 patients with PPM were extracted from the Surveillance Epidemiology and End Results (SEER) database (1975–2016). The chi-square test, paired t-test, and multivariate analysis were used to analyze the data. Results: The majority of PPM patients were male (56.2%, p < 0.005) and Caucasian (90.4%, p < 0.005, with a mean age of diagnosis was 69 ± 13 years. The grading, histological, and tumor size information were classified as “Unknown” in most of the cases, but when available, poorly differentiated tumors (8.7%), malignant mesothelioma, not otherwise specified (63.4%) and tumors > 4 cm in size (8%), respectively, were most common, p < 0.005. Chemotherapy was administered to 50.6% of patients, followed by resection (29.2%) and radiation (1.5%), p < 0.001. The cohort of PPM had a five-year overall survival of 20.3% (±1.1), compared to 43.5% (±5.9), 25.9% (± 8.4), and 18.7% (±1.6) for those with surgery, radiation, or chemotherapy alone, respectively. Poor differentiation (OR = 4.2, CI = 3.3–4.9), tumor size > 4 cm (OR = 3.9, CI = 3.2–4.5), Caucasian race (OR = 2.9, CI = 2.6–4.4), and distant SEER stage (OR = 2.5, CI = 1.1–3.2) were all linked with increased mortality (p < 0.001). Conclusion: An extremely rare and aggressive peritoneal tumor, PPM may be difficult to identify at the time of diagnosis. Radiation therapy likely to have a limited function in the treatment of this condition, with surgery and chemotherapy being the primary choices. All PPM patients should be enrolled in a nationwide registry to improve our understanding of the pathogenesis and identify factors affecting survival.