The natural dyes have numerous advantages with fewer problems like color strength and fastness. Different methods have been extensively studied to make them industrial ready. This study optimizes the microwave-assisted natural dyeing of sustainable hemp/cotton blended fabrics using neem bark extract, while henna (Lawsonia inermis) extract was used as a natural bio-mordant to improve dye fixation and fastness properties. A Box-Behnken design under response surface methodology (RSM) was employed to evaluate the effects of microwave irradiation time (2-6 min), pH (2-6), powder concentration (4-10 g), and salt concentration (3-7 g/100 mL) on color strength (K/S). A quadratic regression model was developed and statistically validated through analysis of variance (ANOVA). The model was found to be highly significant (p < 0.0001) with a high coefficient of determination (R2 = 0.9814), indicating excellent alignment between predicted and experimental values. Among the variables, pH and powder concentration exhibited the most significant influence on K/ S, while salt concentration showed a comparatively minor effect. The response surface analysis revealed that lower pH, moderate levels of powder and salt enhanced dye uptake. Numerical optimization predicted the maximum color strength (K/S = 3.93) at a microwave irradiation time of 4.66 min, pH 2.0, powder concentration of 7.52 g, and salt concentration of 5.15 g/100 mL, with a desirability of 0.96. The model validation confirmed the reliability of the predicted results with minimal error. This work focuses on sustainable hemp/cotton blends and provides a predictive modeling framework for process optimization, which differs from previous works. The findings demonstrate that RSM is an effective tool for optimizing eco-friendly dyeing processes.

microwave-assisted dyeing, natural dye, response surface methodology, neem, sustainable textile processing