The presence of highway work zones has a major effect on safety, mobility, and project expenses. The objective of this study is to develop a multi-objective optimization model to address these challenges by considering all three factors simultaneously. The model employs a Genetic Algorithm to identify the Pareto front and elucidate the trade-offs between safety, mobility, and cost. It evaluates various decision variables related to site geometry, work management, and temporary traffic control measures, exploring numerous potential combinations and offering decision-makers a comprehensive array of solutions. A case study demonstrates the model’s efficacy. Initially, approximately 829,440 feasible solutions were identified, which were effectively reduced to 263 by imposing additional constraints such as specific safety levels, maximum project costs, or traffic delay thresholds. The findings highlight significant cost variations: crash costs ranged from saving USD 973,473 to increasing costs by USD 1,328,322; mobility costs ranged from USD 184,491 to USD 3,854,212; and project costs ranged from USD 1,424,634 to USD 1,574,894. These variations underscore the substantial influence of crash costs and the benefits of location-based scheduling, which improves cost estimate reliability by capturing the effects of working hours and project duration. This research builds upon previous studies by incorporating three distinct objectives rather than focusing on a singular solution. By addressing safety, mobility, and project cost separately, the framework yields multiple solutions, each impacting the objectives differently. This multifaceted approach enhances its utility as a robust decision-making tool for stakeholders involved in highway work zone management and planning. This study concludes that multi-objective optimization is crucial for providing realistic and diverse solutions, ultimately improving decision-making processes in highway work zone operations.