The sustained deterioration of the freeway infrastructure of a nation has resulted in an increase in the number, duration, and scope of maintenance projects. In order to enhance the mobility and safety of freeway segments plagued by work zone activities, transportation agencies and professionals have been exploring the potential benefits of efficient and economical maintenance scheduling. This thesis proposes systematic methodology for the optimization of work zone scheduling based on analytical and simulation models to estimate total project cost. Multi-regression models were developed using microsimulation and embedded them into the costs models and costs were predicted. Solver optimizer was used to find the optimal start and end times, productivity indices, and corresponding sub-sectional lengths of project by minimizing the total project cost. Case studies were conducted to assess the performance of the proposed methodology. Lastly, conclusions were made to support transportation agencies in the development of work zone management plans.