Vehicle routing is a critical factor in municipal solid waste (MSW) collection planning and operations. Poor routing can introduce inefficiencies and cause targeted levels of services or performance to be missed irrespective of the level of resource application. Trial and error approaches have been proven to be not the best in the planning and prediction of expected performance. This study explores various Geographic Information System (GIS) tools and analysis techniques, and how they can be applied to optimizing vehicle routes in light of challenging site conditions. Using Adentan West residential area, suburb of Accra Ghana as a case study, current performance of the trial and error method was measured and a GIS computer model was used to evaluate various optimization scenarios to determine the level of savings that can be made. Field measurements were taking with Global Positioning System (GPS) devices for waste collection activities in areas with varying characteristics and conditions, and data analysed for one selected vehicle operating four days per week. It was found that, for a scenario where only the bin collection order was optimized while route selection was restricted by the ArcGIS Network Analyst, 2.6% of travel distance and 2.21% of travel time were saved. For the second scenario where only the route selection was optimized while order of bin collection was restricted, 4.1% and 1.5% of travel distance and time respectively were saved. For a third scenario where both the order of collection and route selection were together optimized, 10.9% and 3.7% of travel distance and time respectively were saved. Lastly, by regrouping all the bins for daily collection, 4.5% and 1.2% of travel distance and time respectively were saved. The results demonstrated that there is always room for optimization of solid waste collection routing irrespective of site constraints and other challenges that the nature of bin distribution pose to drivers. In developing countries like Ghana, where there is high demand for services in the face of limited road network access, application of GIS in optimization of routes will guide providers in planning and subsequently make more savings in fuel consumption, vehicle maintenance and cost of man-hours.