Infrastructure is a significant element in an effort to improve nation's competitiveness at the global scale. As a developing country, Indonesia currently attempts to improve the quality and expand the quantity of its infrastructure by initiating mega project infrastructure, e.g. Trans-Sumatera Toll Road. The project located in the western part of Indonesia, in Sumatera Island. It connects Lampung province to Aceh province for about 2,788 km. Although the project will substantially increase the economic activities of people, the amount of investment is relatively huge. It requires approximately 340 trillion rupiahs or equal to US 24.29 billion only for the construction. Thus, route planning in the initial stage shall be comprehensively investigated to produce higher benefits over cost. The purpose of this research is to develop alternative route planning for Trans-Sumatera Toll Road by taking into account the southern part of Sumatera as the case study. Quantitative and qualitative approaches were to achieve project objectives through in-depth interview and financial analysis. This findings show that the southern part of Sumatera has potential contribution to the regional economic activities and national growth. The result also generates potential featured sectors for each province such as mining and quarrying, agriculture, fishery, and so on. Initial cost for the alternative route in the southern part of Sumatera is estimated about 120.85 trillion rupiahs or equal to US 8.95 billion.