Local site effect is an important feature of seismic hazards, which often causes amplification of ground motions and results in increasing the damage potential of earthquake. This paper presents an experimental study of microtremor data to investigate the dynamic characteristics of soil and structures at the 15th May City, southeast Cairo, Egypt. This city was constructed on Eocene sedimentary rocks of mainly limestone. Despite the newness of this city, their buildings suffer from structural damages, which mainly developed over the last two decades. Predicting the reasons of structural damage caused by earthquakes (including micro-earthquakes) is considered and became the main target of this study. The horizontal vertical spectral ratio (HVSR) analyses of ambient noise data at 54 sites were processed and interpreted using Geopsy Software to calculate the amplification factor and fundamental resonance frequency of each observation point. Three tests including the damping value, the horizontal spectrum rotate, and H/V rotate were undertaken to ensure that the peaks of spectral ratio are either natural or artificial origin. The vulnerability index (Kg) was estimated based on Nakamura’s technique for assessing the seismic vulnerability index (SVI). The results indicate that the resonance frequency ranges between 1.36 and 1.607 Hz at the most measured stations, but it attained higher value up to 11 Hz at sites having high thicknesses of soft sediments. The lowest resonance frequencies occur in the areas of the deepest bedrock, whereas the higher resonance frequencies were observed in the areas of shallowest bedrock. The amplification factor ranges between 1.09 and 3.61 at most measured stations, but it became greater up to 5 in few locations. The northern west part of the area has thick soft sediments and may be more affected by earthquake damage because it contains SVI values ranging from 6.5 to 8.5, in consistent with the amplification factor and fundamental frequency results, while the other parts of the area are relatively safe because they contain low SVI values (0.5–4.3).