Interlocking intramedullary nailing and percutaneous plate implantation are commonly used techniques in the treatment of femoral shaft fractures. This study aimed to determine the most appropriate and effective treatment strategy between interlocking intramedullary nails and percutaneous plate implantation by analyzing and summarizing the available evidence. Relevant articles published from the date of database construction in PubMed, Embase, Web of Science, and Cochrane to 2024 were searched and downloaded according to PRISMA 2020. These studies were screened following pre-established inclusion criteria, and the data were extracted. Methodological quality assessment for retrospective studies was performed using the Newcastle-Ottawa Scale, whereas Review Manager Software was used for methodological quality assessment of randomized controlled trials (RCTs) and statistical analysis. Only 13 studies containing 1061 patients were included in the meta-analysis. Femoral shaft fractures treated with interlocking intramedullary nailing had shorter operative and fluoroscopic time and less estimated blood loss. Pediatric patients treated with interlocking intramedullary nails had less estimated blood loss and shorter healing time. Interlocking intramedullary nailing group in the retrospective study was associated with shorter operative time and less blood loss, whereas, in the randomized controlled trial (RCT) study, it was associated with less blood loss and shorter healing time. Interlocking intramedullary nailing is more advantageous in treating femoral shaft fractures and is a more appropriate option for treating femoral shaft fractures in pediatric patients. PROSPERO: CRD42024564563.