The low-cost and small size solid-state sensor arrays are suitable to implement a wide-area electronic nose (e-nose) for real-time air quality monitoring. However, accuracy of these low-cost sensors is not adequate for precise measurements of pollutant concentrations. Artificial neural network (ANN) estimation models are used for the soft calibration of low-cost sensor array measurements and significantly improve the accuracy of low-cost multi-sensor measurements. However, optimality of neural architecture affects the performance of ANN estimation models, and optimization of the ANN architecture for a training data set is essential to improve data-driven modeling performance of ANNs to reach optimal neural complexity and improved generalization. In this study, an optimal architecture ANN estimator design scheme is suggested to improve the estimation performance of ANN models for e-nose applications. To this end, a gray wolf optimization (GWO) algorithm is modified, and an exploitative alpha gray wolf optimization (EA-GWO) algorithm is suggested. This modification enhances local exploitation skill of the best alpha gray wolf search agent, and thus allows the fine-tuning of ANN architectures by minimizing a multi-objective cost function that implements mean error search policy. Experimental study demonstrates the effectiveness of optimal architecture ANN models to estimate CO concentration from the low-cost multi-sensor data.