ABSTRACT The remarkable mechanical properties of high-performance concrete (HPC) make it indispensable in a wide range of engineering applications. Predicting HPC’s compressive strength with precision is essential to guaranteeing its structural stability and longevity. The present work introduces a novel method for predicting HPC compressive strength (CS) by utilizing the Multi-layer Perceptron (MLP) model in conjunction with three distinct optimizers, namely Northern Goshawk Optimization (NGO), Manta Ray Foraging Optimization (MRFO), and Atom Search Optimization (ASO). An effective method for capturing complex relationships between input and output variables is the multi-layer perceptron (MLP) in artificial neural networks. Developing a dependable, robust predictive model is the goal of training the MLP model on a variety of datasets of HPC mixtures and CS. As evidenced by the MLNG model’s R2 value of 0.994 and RMSE of 1.3572, the joint efforts of MRFO, NGO, and ASO during the optimization phase improve the MLP model and produce promising results. These results clarify how different optimizers play a crucial role in improving the accuracy of HPC compressive strength predictions made with the MLP model. This information helps make better decisions regarding design and construction methods for HPC.