Although cities cover only less than 1% of the land surface, 50% of world population are living in urban areas that include more than 70% of the economic activities and use 75% of the world resources. Population, economy, transportation, and policies factors are identified as the main factors that affect urban expansion and development, especially in developing countries. Political transformations and instability conditions are among the most important factors effecting social, economic, and environmental aspects in the world especially in the countries and regions witnessed wars and political problems. In Occupied Palestinian Territories (OPT) the rapidly growing population, limited available decisions of policy makers, and political instability played a main role in the Palestinian urban expansion and development. Therefore, this study aims to define the most suitable area that should be developed in the Southeastern Jerusalem Region (SERJ) living under political instability conditions. Integrated the Geographical Information System (GIS) with Multi-Criteria Evaluation approach (MCE) Conducted to find the potential areas to be considered as urban development areas in the region. The modeling and analysis indicates four suitable classes and areas: highly suitable, highly moderate, suitable, and low suitable. Suitability map of urban expansion and development shows 77% of the study area consists of low suitable areas that are distributed in north and east of SERJ. The Palestinian urban policy makers need to pay more attention to urban development and expansion in the Southeastern Jerusalem Region because these areas are so close to the Jerusalem city in the west, and it is the last pass-point in the west bank between the north and the south. Policy makers, urban planners, urban mangers, and people need to show more awareness towards the sustainability urban planning issues, especially during political instability stages. Principles of urban smart growth will be useful ideas for promoting the sustainability in the Palestinian urban environments.