Solid waste management is critical to sustainable, healthy, and eco-friendly cities and societies. In developing countries, only a small percentage of municipal solid waste is disposed safely, while the majority remains in the streets or disposed in open landfills. Most countries seek to establish effective and efficient solid waste management system (SWMS) that can handle and dispose of the daily generated waste at minimum cost and in a sustainable manner. Those systems usually consist of waste sources, waste collection stations, landfills, incinerators, and recycling plants, in addition to the transportation system that integrates the different sub-systems. The problem facing decision-makers while designing or reconfiguring a SWMS is to determine the optimal supply chain network design for such systems in a way that ensures the treatment and disposal of all daily generated waste at the lowest cost. In this context, this paper aims to develop a generic optimization model suitable for application in SWMS optimization in developing countries. A new mixed-integer linear programming (MILP) model is formulated for a SWMS configuration that integrates waste generation sources, collection/transfer stations, recycling plants, incinerators, and landfills. The proposed MILP model is formulated to determine the optimal number and locations of the different facilities, and the optimal flow of waste in the system that minimizes the net daily cost incurred in the system. The model has been applied in a case study on the SWMS in Fayoum Governorate, Egypt. The main contribution of this research refers both to the theoretical development of a generic MILP model that can be applied to optimally design the SWMS in developing countries, and to its operational counterpart, as per the design solutions provided in the SWMS of Fayoum Governorate (Egypt).