Chest diseases, especially COVID-19, have quickly spread throughout the world and caused many deaths. Finding a rapid and accurate diagnostic tool was indispensable to combating these diseases. Therefore, scientists have thought of combining chest X-ray (CXR) images with deep learning techniques to rapidly detect people infected with COVID-19 or any other chest disease. Image segmentation as a preprocessing step has an essential role in improving the performance of these deep learning techniques, as it could separate the most relevant features to better train these techniques. Therefore, several approaches were proposed to tackle the image segmentation problem accurately. Among these methods, the multilevel thresholding-based image segmentation methods won significant interest due to their simplicity, accuracy, and relatively low storage requirements. However, with increasing threshold levels, the traditional methods have failed to achieve accurate segmented features in a reasonable amount of time. Therefore, researchers have recently used metaheuristic algorithms to tackle this problem, but the existing algorithms still suffer from slow convergence speed and stagnation into local minima as the number of threshold levels increases. Therefore, this study presents an alternative image segmentation technique based on an enhanced version of the Kepler optimization algorithm (KOA), namely IKOA, to better segment the CXR images at small, medium, and high threshold levels. Ten CXR images are used to assess the performance of IKOA at ten threshold levels (T-5, T-7, T-8, T-10, T-12, T-15, T-18, T-20, T-25, and T-30). To observe its effectiveness, it is compared to several metaheuristic algorithms in terms of several performance indicators. The experimental outcomes disclose the superiority of IKOA over all the compared algorithms. Furthermore, the IKOA-based segmented CXR images at eight different threshold levels are used to train a newly proposed CNN model called CNN-IKOA to find out the effectiveness of the segmentation step. Five performance indicators, namely overall accuracy, precision, recall, F1-score, and specificity, are used to disclose the CNN-IKOA’s effectiveness. CNN-IKOA, according to the experimental outcomes, could achieve outstanding outcomes for the images segmented at T-12, where it could reach 94.88% for overall accuracy, 96.57% for specificity, 95.40% for precision, and 95.40% for recall.