Groundwater is the main resource for irrigation and drinking supply in most parts of Syria, as for most Mediterranean countries, however this resource suffers from mismanagement. In the study area (northeast of Mt. Hermon), the lack of information makes water management in this area extremely difficult. Assessing groundwater pollution risk is the most essential issue for water resources management, especially in the regions where complex interaction between climate, geology, geomorphology, hydrogeology, water scarcity and water resource mismanagement exist. This complexity leads to significant complication in determining pollution risk of studied system. In the present work, we adopted an integrative approach to assess groundwater pollution risk in the study area. This methodology is based on the analysis of hydrogeological characteristics of aquifer systems and the available information about socioeconomic context and physiochemical groundwater conditions that might affect this system. This approach allowed us to delineate the groundwater pollution risk map based on the analysis of concerning parameters/indicators. The degree of risk was assessed as the sum and average of rating of these parameters and indicators for each subarea. Typically, very high pollution risk index was identified over the Quaternary/Neogene horizon, i.e., shallow and unconfined aquifer and in the lower part of Jurassic aquifer. In these two parts, the majority of anthropogenic activities are concentrated. Low pollution risk index was found for the outcropping of low permeable Quaternary basalt at the Southern part of the study area. A moderate pollution index was identified for the low/moderate permeability of silt, clay and marly limestone-rich horizons of the major part of Neogene aquifer outside of the intersected zones with Quaternary aquifer and for the Paleogene formations. The spatial analysis shows that about 50% of the study area is characterized as being at very high and high pollution risk index. Hence, the overall natural protective capacity of this area is still poor. This study demonstrates the flexibility of the proposed approach to assess groundwater pollution risk in local complex aquifer system characterized by lack of information and data in order to reduce the risk of future groundwater pollution.