OBJECTIVES: We sought to collate and summarize high-quality data on non-typhoidal Salmonella invasive disease (iNTS) incidence to provide contemporary incidence estimates by location and year. METHODS: We systematically searched the databases Embase + MEDLINE, Web of Science, and PubMed for articles published on the incidence of iNTS from inception of the database through 8 May 2020 with no language, country, date, or demographic restrictions applied. A meta-analysis was performed to report pooled iNTS incidence as a rate of cases per 100,000 per year. RESULTS: Among 13 studies eligible for analysis, there were 68 estimates of incidence. Overall pooled incidence (95% CI) was 44.8 (31.5-60.5) per 100,000 persons per year. When stratified by region, pooled incidence was significantly higher in Africa than Asia, 51.0 (36.3-68.0) compared to 1.0 (0.2-2.5), respectively. Incidence was consistently higher in children aged <5 years compared with older age groups. Incidence displayed considerable heterogeneity in both place and time, varying substantially between locations and over consecutive years in the same location. CONCLUSIONS: iNTS incidence varies by region, location, age group, and over time. Concerted efforts are needed to address the limited high-quality data available on iNTS disease incidence.