Understanding spatial patterns of environmentally sensitive areas (ESAs) to desertification is essential for sustainable land use in the drylands. This work is a novel trial for integrating the erosion quality index (EQI) with a modified Mediterranean Desertification and Land Use (MEDALUS) method and factor analysis to define ESAs to desertification. The model was then applied within 8607.13 km2 (860713 ha) in the north Nile Delta of Egypt as a case study. Climate data, satellite imageries, field observations, and samples collected from 105 soil profiles were analyzed to characterize five thematic quality indices of soil, climate, vegetation, management, and erosion. These indices were weighted based on the factor analysis (FA) and superimposed under the GIS environment in a single map using the weighted sum model. The proposed model showed that 72% of the total area was classified as critical-sensitive to desertification where 70% was classified as highly-critical, while 2% as moderately-critical. No significant difference (p < 0.001) was observed between the results of the proposed model and those calculated by the geometric mean algorithm (MEDALUS model) with R2 and root mean square error of 0.88 and 0.11, respectively. The average linear sensitivity analysis showed that using weights derived from the FA could assimilate the results of the proposed model closer to reality rather than equal weights used in the MEDALUS model. The developed model would improve the insight into desertification processes in the studied area, thereby suitable conservation practices would be adopted in time.