Background: Curative management of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiation therapy (nCRT) followed by radical surgery. Pathological complete response (pCR) is seen in 15-27% of patients. The response to nCRT may be influenced by genetic variations. Gene signatures therefore may serve as biomarkers for predicting response or resistance to nCRT. We conducted a systematic review on genetic biomarkers for response prediction to nCRT in LARC and identify common genes or ontology pathways. Methods: A systematic search of electronic databases (MEDLINE, PubMed and EMBASE) was performed for relevant recent studies. Studies were screened as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with search terms “rectal neoplasm”, “rectal cancer”, “gene”, “gene expression”, “gene expression profile”. The relevant studies were selected for full-text review. Studies that reported gene expression profile to predict response to nCRT were included. Results: Twelve of 367 studies screened were included. Most studies used microarray or real-time reverse transcription PCR. Six of these assessed for gene predictors of pCR with 2 studies reporting correlation between certain genes and pCR: thymidylate synthetase; gene set (including LMNB2, MLF2, DDX1, EIF4A1, FOXO3A, ILF3 and SEMA3C); 19 genes including (NPSR1, HYAL1, FGFBP1, PLLP and MALL). Common gene ontology pathways identified included DNA break repair via homologous recombination and apoptotic pathways. Conclusions: Multiple genes were identified as prospective biomarkers for nCRT in LARC patients. Further studies are required to validate these identified genes to personalize treatment for LARC patients.