This study develops an integrated model of statistical process monitoring and maintenance policy (MP) for a two-stage cascade process, involving two machines in series where the output of one stage affects the next stage. Instead of a single assignable cause (AC) affecting the quality characteristic, this production process experiences multiple ACs to more precisely simulate real conditions. Traditional and Hotelling’s T2 charts cannot detect the specific stage in which a shift occurs; therefore, this study employs a Cause-selecting control chart. The possibility of equipment failure and system stoppage are considered, with the process failure mechanism following a Weibull distribution. Depending on the conditions affecting the process or equipment, four MPs are considered to acheive the system’s initial condition, resulting in sixteen defined scenarios. The goal is to determine decision variables by minimizing a cost function subject to some statistical measures. This economic-statistical design can improve statistical and/or economic measures. However, it creates a more complex problem. Due to this complexity, a particle swarm optimization algorithm is used for optimization. The proposed model is implemented for a system that produces cotton yarn, with fiber length and skein strength are as the outputs of the first and second stages, respectively. Comparisons with two models validate the proposed model’s performance in cost reduction. A sensitivity analysis is performed for further investigations. The results indicate significant cost savings of the proposed model.