This study presents an innovative methodology for Highway Route Selection (HRS), specifically tailored for mountainous terrains. The approach focuses on selecting the most suitable route for road alignment while prioritizing road safety and hydrological and geological considerations. Through systematic analysis, the methodology evaluates alternative road alignments by examining various risk factors related to geometric design, hydrological, and geological impacts. Utilizing Fault-Tree Analysis (FTA), 14 key design factors related to geometric design and environmental factors are identified. The results demonstrate the effectiveness of the methodology in selecting road alignments that enhance safety and mitigate environmental risks. A case study is presented where a 90-km segment of a road in Egypt’s Golden Triangle Project, characterized by challenging terrain and diverse geological features, is examined. Through detailed analysis, the study identifies critical design factors to enhance road safety and minimize environmental impact. The methodology’s comprehensive approach offers insights into road design, providing a quantitative framework for decision-making and mitigation strategies.