A systematic review was conducted to identify the biological responses, allergic reaction, hypersensitivity, toxicity, and ion release profile associated with pediatric stainless steel crowns (SSCs) in the existing literature. A systematic search was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The inclusion criteria consisted of patients younger than 20 years of age with SSC placement on primary or permanent teeth and in vivo and in vitro exposure to SSCs. Outcomes measures included adverse oral/mucosal effects; removal/failure/replacement of the SSC; type of allergic reaction; nickel (Ni) or other ion levels in bodily fluids, cellular, genotoxic, cytotoxic, mutagenic or carcinogenic effects related to the SSC. After an initial search of 764 studies in the database, 17 articles were included in the analysis. Evidence of allergic reactions to SSCs in children is limited and obtained from mostly low-quality research. Some studies showed that the amount of Ni detected was less than the amount ingested in the daily diet. In contrast, other studies reported a significantly higher release of Ni occurred into the saliva in acidic environments. There is some concern about the leaching of metal ions such as Ni from SSCs in children at high risk for caries. Further long-term studies are required to investigate this phenomenon.