Because of fast urban sprawl, land use competition, and the gap in available funds and needed funds, municipal decision makers and planners are looking for more cost-effective and sustainable ways to improve their sewer infrastructure systems. The dominant approaches have turned to planning the sanitary sewer systems within a regional context, while the decentralized and on-site/cluster wastewater systems have not overcome the application barriers. But regionalization policy confers uncertainties and risks upon cities while planning for future events. Following the philosophy of smart growth, this paper presents several optimal expansion schemes for a fast-growing city in the US/Mexico borderlands—the city of Pharr in Texas under uncertainty. The waste stream generated in Pharr is divided into three distinct sewer sheds within the city limit, including south region, central region, and north region. The options available include routing the wastewater to a neighboring municipality (i.e., McAllen) for treatment and reuse, expanding the existing wastewater treatment plant (WWTP) in the south sewer shed, and constructing a new WWTP in the north sewer shed. Traditional deterministic least-cost optimization applied in the first stage can provide a cost-effective and technology-based decision without respect to associated uncertainties system wide. As the model is primarily driven by the fees charged for wastewater transfer, sensitivity analysis was emphasized by the inclusion of varying flat-rate fees for adjustable transfer schemes before contracting process that may support the assessment of fiscal benefits to all parties involved. Yet uncertainties might arise from wastewater generation, wastewater reuse, and cost increase in constructing and operating the new wastewater treatment plant simultaneously. When dealing with multiple sources of uncertainty, the grey mixed integer programming (GIP) model, formulated in the second stage, can further allow all sources of uncertainties to propagate throughout the optimization context, simultaneously leading to determine a wealth of optimal decisions within a reasonable range. Both models ran for three 5-year periods beginning in 2005 and ending in 2020. The dynamic outputs of this analysis reflect the systematic concerns about integrative uncertainties within this decision analysis, which enable decision makers and stakeholders to make all-inclusive decisions for sanitary sewer system expansion in an economically growing region.