Background: Preserving vital pulp tissue in immature permanent molars affected by deep caries is essential to encourage continued root maturation. Mineral trioxide aggregate (MTA) is a standard biomaterial, but alternatives like melatonin offer anti-inflammatory and odontogenic potential. This randomized clinical trial aimed to evaluate and compare clinical and radiographic outcomes following apexogenesis using melatonin, MTA, and their combination. Methods: Forty-five immature mandibular permanent first molars in children aged 6–8 years were randomly assigned to three groups (n=15 each): Group A (MTA), Group B (melatonin), and Group C (MTA + melatonin). Clinical parameters (pain, mobility, mucobuccal fold changes) and standardized digital radiographic outcomes (root lengths, apical foramen width, radicular dentin thickness, furcation radiodensity) were recorded at baseline, 1, 3, 6, 9, and 12 months post-operatively. Statistical evaluation included repeated-measures ANOVA, non-parametric tests, and Pearson correlation analysis. Results: High clinical success was observed at 12 months: Group C achieved 100%, while Groups A and B achieved 93.3% each, with no statistically significant intergroup differences. All successful cases showed continued apexogenesis. Pearson correlation and heatmap analysis demonstrated significant positive correlations between root length, dentin thickness, furcation radiodensity, and follow-up time. Root lengths correlated negatively with pain and mobility. Isolated failures revealed minor temporal discrepancies: MTA exhibited early clinical pain prior to radiographic signs, while melatonin presented radiographic arrest with minimal pain. Conclusions: Melatonin demonstrates clinical and radiographic efficacy comparable to MTA in apexogenesis. High concordant correlation confirms that clinical symptom resolution reliably mirrors radiographic physiological root development.