The influence of lateral heterogeneities on alluvial deposits is a topic of particular interest in the field of urban planning and engineering design of structures and infrastructures. This work focuses on the effects of such heterogeneities on the shear strains produced within the recent alluvial deposits of the Tiber River in the historical center of Rome in case of the worst expected earthquake scenario. To this aim, a 3D engineering‐geology model of the subsoil is used to derive four geological sections across the Tiber River valley as well as 48 soil columns to perform numerical simulations. Various models are considered: a viscoelastic equivalent linear rheology in a 1D finite‐difference model for one‐component horizontal input, a nonlinear elastoplastic model in a 1D finite‐element scheme for three‐component input, and a nonlinear viscoelasto‐plastic rheology in a 2D finite‐difference model under one‐component horizontal input. After comparing these different simulations, results have shown that lateral heterogeneities play a key role with respect to the expected shear strains within multilayered soils. To this aim, some specific indexes are introduced to estimate the maximum shear strain (MSS) concentration within the soil layers as well as to highlight their effect due to the stratigraphic position of the layers, within the soil column, independently from its depth. A final differential index leads to the evaluation of the lateral heterogeneity effect on the estimated MSS, demonstrating their prevalent role with respect to the bedrock shape (i.e., the angle of inclination of the buried valley slopes). From these results, an MSS zoning map is obtained for the historical center of Rome, showing that the local seismic response should be modeled by assuming 1D or 2D conditions depending on the location considered.