Abstract Background Staphylococcus aureus (S. aureus) is a bacterium of public health importance. The zoonotic spread of this pathogen through animal-derived foods has been reported. This systematic literature review investigates the prevalence, distribution, antimicrobial resistance (AMR) profiles, and molecular characteristics of S. aureus in the food chain in Nigeria. Methods A systematic search of online databases (Pub Med, Google Scholar, and Web of Science) for published articles from January 2002 to January 2022 was performed using the Prisma guideline. Results Fifty articles were included from an initial 511 extracted documents. These papers included research carried out in 22 states across Nigeria. S. aureus detection in most studies was above the satisfactory level for foods (≥ 104 CFU/g). The prevalence of S. aureus ranged from 1.3% in raw cow meat to 72.5% in fresh poultry meat. Most S. aureus isolates demonstrated multiple drug resistance patterns, especially being resistant to beta-lactams. There is a lack of information on the molecular typing of the S. aureus isolates. The different spa types of S. aureus isolated were t091, t314, t1476, and t4690, categorized into Multi-Locus-Sequence Types ST8, ST121, ST152, and ST789. Virulence genes detected include pvl, sea, see, spa, coa, edin, tsst, and hly. Certain AMR-encoding genes were detected, such as mecA, blaZ, fos, tet, and dfsr.. Factors contributing to the presence of S. aureus were reported as poor processing, poor sanitary conditions of the food processing units, inadequate storage units, and poor handling. Conclusion We showed that S. aureus is a major food contaminant in Nigeria despite the need for more information on the molecular typing of strains from animal-derived food sources. There is a need to control S. aureus by targeting specific entry points based on the findings on risk factors and drivers of food contamination.