Background: Gastric and EGJ cancer in Latin America are associated with a high burden of disease and mortality. Treatment with combination chemotherapy (CT) is the current standard of care for metastatic disease, but with poor benefit. ICI appears as a new option in this setting improving survival and no local guidelines have been found addressing this issue. Methods: We carried out a comprehensive systematic review up to August 2021 and meta-analysis according to PRISMA guidelines and used the GRADE approach to summarize each question in evidence tables. Judgments regarding risk of bias, precision, consistency, directness, and likelihood of publication bias were made and categorized into 4 levels of evidence’s certainty ranging from very low to high. SLAGO formed a guideline panel composed of medical professionals from 6 countries in Latin America and prioritized 2 relevant questions. We provided de novo recommendations for the local setting using the Evidence-to-Decision (EtD) frameworks provided by GRADE to discuss benefits and harms, values and preferences, use of resources, feasibility, acceptability, and equity. Results: The panel agreed on 3 recommendations. For question 1, regarding the use of CT+ICI vs CT, the global certainty of evidence was rated as high. For question 2 (CT vs ICI), the global certainty of evidence was rated as low due to imprecision. The recommendation for question 1 was conditional for the use of CT+ICI among the population with CPS > 1 and strong among those with CPS > 5. For question 2, the recommendation was conditional against the treatment with ICI, regardless of CPS score. Concerns about the lack of economic evidence addressing the treatment's cost-effectiveness were identified. The panel highlighted the complexity of the Latin America health systems for the implementation of CT+ICI and its equity impact. Finally, some research priorities were highlighted (effectiveness in HER2+, CPS 1-4, or MSI-H tumours). Conclusions: The panel agreed on the net clinical benefit of CT+ICI for selected patients (CPS > 5). Nonetheless, cost-effectiveness data are still lacking, especially in Latin America.