This article presents a comprehensive framework for determining the location of road weather information system (RWIS) stations over a regional road network. In the proposed methodology, the region is divided into a grid of equal-sized zones which are considered as the minimum spatial unit for allocating a candidate set of RWIS stations. These zones are ranked according to a set of pre-specified criteria that reflect the needs for, and potential benefits from, real-time road weather information, including road surface temperature variability, precipitation, network traffic, and collision patterns. A case study based on the existing RWIS network in the province of Ontario was conducted to illustrate the major features of the proposed method and evaluate the implications of alternative location selection criteria. The findings of the study suggest that it is feasible to develop a systematic process for locating RWIS stations using an integrated location criterion to capture multiple factors being considered in practice. The study has also revealed the need to establish quantitative models for estimating the benefit of real-time information from RWIS stations, which is the foundation of a cost–benefit-based RWIS location optimization model.