Background: Keloids are benign fibrous growths resulting from abnormal wound healing, commonly affecting individuals with darker skin tones. Genetic factors, particularly the Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 4 (NEDD4) gene transcript variant 3 (NEDD4-TV3) and growth factors like insulin-like growth factor-1 (IGF-1), are implicated in keloid formation. Objective: This study aimed to assess the expression levels of NEDD4-TV3 and IGF-1 in keloid tissue and their potential role in keloid pathogenesis. Patients and methods: This case-control study was conducted involving 30 keloid patients and 20 individuals of matched age, sex and BMI as a control group. Comprehensive history, examination, and laboratory investigations were performed, including PCR for NEDD4-TV3 and IGF-1 gene expression. Results: NEDD4-TV3and IGF-1 gene expressions were significantly higher in keloid patients compared to controls (P ≤ 0.001). NEDD4-TV3 ≥75852 predicted keloid formation with 95% sensitivity, 95% specificity, 97.4% PPV, 90.5% NPV, and 95% accuracy (AUC = 0.983, 95% CI: 0.95-1.0). IGF ≥8490 had 77.5% sensitivity, 70% specificity, 97.4% PPV and 90.5% NPV. NEDD4-TV3 significantly correlated positively with pigmentation score, vascularity score, height score, total Vancouver scale (P ≤ 0.001) for all, and IGF-1 expressions (P = 0.014). IGF-1 significantly correlated with pigmentation score, vascularity score, and total Vancouver scale (P = 0.03, 0.016, 0.005) respectively. Conclusions: Significantly elevated NEDD4-TV3 and IGF-1 gene expressions were associated with increased susceptibility to keloid formation, suggesting their potential role in keloid etiopathogenesis and their predictive roles.