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Using published cross-sections and a series of geological constraints, a 3D geological model of an important area of the Adriatic sector of peninsular Italy—i.e., the Marche region—was developed. Then, an analytical procedure, taking into account the heat rising from the mantle and the radiogenic heat produced by the crust, was applied on the pre-built structural model, in order to obtain the 3D geothermal setting of the entire region. The results highlighted the key role played by the Moho geometry, particularly as a step of ~10 km occurs between the Adriatic Moho of the subducting plate to the west and the new Tyrrhenian Moho characterizing the back-arc area to the west. The comparison between our results and available borehole data suggests a good fit between the applied analytical methodology and published datasets. A visible anomaly is located at a specific site (i.e., the coastal town of Senigallia), where it may be envisaged that fluid circulation produced a local surface heat flow increase; this makes the Senigallia area a promising feature for the possible exploitation of geothermal systems. [ABSTRACT FROM AUTHOR]