The rapid growth of electronic commerce is having an impact on the way urban logistics are organized. In metropolitan settings, the last-mile delivery problem, i.e., the problem regarding the final stage of delivering a shipment to a consumer, is a major concern due to its inefficiency. The development of a convenient automated parcel lockers (APLs) network improves last-mile distribution by reducing the number of vehicles, the distances driven, and the number of delivery stops. Using automated parcel lockers, the last-mile issue could be overcome for the environment’s benefit. This study aimed to define and validate an APL network containing hundreds of APLs with the use of an example made up of real case study data from the city of Poznań in Poland. The goal of this research was to use mathematical programming for optimization and simulation to tackle the facility location problem for automated parcel lockers through a practical approach. Multi-criteria simulation-optimization analysis was used to assess the data. In fact, the simulation was carried out using Anylogic software and the optimization with the use of the Java programming language and CPLEX solver. Three years were simulated, allowing for comparable results for each year in terms of expenses, e-shoppers, APL users, and demand evolution, as well as achieving the city’s optimal locker usage. Finally, encouraging conclusions were obtained, such as the relationship between the demand and the number of lockers, along with the model’s limitations.