<p>The construction industry is under increasing pressure to reduce its environmental footprint, particularly because of the high carbon emissions associated with cement production. In response, this study explores the development of more sustainable concrete by partially replacing cement with waste glass powder (WGP) and nano-silica (NS) powders. These materials, both industrial byproducts, offer promising pozzolanic activity and microstructural benefits; however, their combined effects on concrete performance have not been fully optimised. To address this, we employed a Taguchi L16 experimental design to systematically vary the proportions of WGP (0–20%), NS (0–4%), and cement (50–65%) to evaluate their influence on compressive strength, tensile strength, flexural strength, workability, and water absorption. The optimised mix, comprising 15% WGP, 3% NS, and 50–55% cement, achieved a peak compressive strength of 47.5&#xa0;MPa and a minimum water absorption rate of 2.6%, reflecting a balanced improvement in both strength and durability. Workability improved with increasing WGP but declined with higher NS content owing to its fine particle size and water demand. To validate the findings, we trained artificial neural network (ANN) and support vector regression (SVR) models using 16 experimental data points, which were split into training (70%), validation (15%), and testing (15%) sets. The ANN model achieved superior predictive accuracy (R² &gt; 0.92), confirming the robustness of the experimental outcomes. Based on these results, we recommend the adoption of a 15% WGP and 3% NS mix for practical use in sustainable construction. This approach not only reduces cement consumption and repurposes industrial waste but also offers a data-driven solution for producing high-performance, eco-friendly concrete.</p>