<p>The utilization of industrial waste as supplementary cementitious materials offers a sustainable approach to reducing cement consumption while enhancing concrete performance. This study investigates the synergistic effect of ceramic powder (CP) and nano-silica (NS) as partial replacements of cement in concrete. Nano-silica was maintained at a constant dosage of 2%, while ceramic powder was varied from 0% to 20% by weight of cement. Mechanical properties were evaluated through compressive, split tensile, and flexural strength tests at different curing ages. Durability was assessed using ultrasonic pulse velocity, rapid chloride penetration, and drying shrinkage tests. In addition, the flexural behavior of reinforced concrete beams was examined under two-point loading. Microstructural characteristics were analyzed using scanning electron microscopy and energy-dispersive spectroscopy. To support experimental findings, machine learning models including Random Forest, Support Vector Machine, and Artificial Neural Network were developed for strength prediction, achieving high predictive accuracy (R² ≈ 0.97). To enhance the reliability of the machine learning model, the experimentally collected dataset was further expanded by physics-guided interpolation and controlled stochastic perturbation while upholding the discovered material trends. Results indicate that the mixture containing 15% CP and 2% NS provides superior mechanical, durability, and structural performance, demonstrating the potential of these materials for sustainable and data-driven concrete design.</p>