<p>Concrete is one of the essential construction materials that play a vital role in the country’s economic development and improved lifestyle of the people. Nanocomposite concrete is another innovative material that enhances strength with minimal additions, reducing environmental harm from excessive cement production. The study employs the Design of Experiments (DOE) to simplify and optimize the study of sustainable Nanoconcrete. Further, this study used Response Surface Methodology (RSM) to optimize and predict the compressive strength of M20 concrete incorporating nanomaterials and electronic waste. The optimization process involves identifying seven key controllable factors, including type of cement, aggregates, water-cement ratio, nanomaterials, and curing duration. Using DOE, 13 sample combinations were selected for 7-day testing and another 13 for 7, 14, and 28-day curing. Concrete mixes included partial replacement of coarse aggregates with 20% e-waste and cement substitution with nanomaterials like CNTs, nanosilica, nanoclay, and TiO₂ at optimized dosages. Maximum replacement of 3% TiO₂, 0.1% CNT, 3% nanoclay and 1% of nanosilica used in this research. The models demonstrated high accuracy, with a maximum error of 3.64% for 7-day compressive strength, outperforming previous studies with 5.21% error and for all days test error is 11.31%. Including nanomaterials, particularly TiO₂, CNT, Nanoclay, and Nanosilica, positively impacted concrete strength. Diagnostic plots and optimization tools validated the robustness of the models, highlighting their practical applicability for predicting compressive strength. Through the application of RSM, this research seeks to develop predictive models that elucidate the complex relationships between nanomaterials and compressive strength of the concrete.</p>