Purpose Localization and quali-quantitative characterization of radionuclide-contaminated soils are essential for healthcare and remediation activities. However, characterization activities are at the moment mainly based on very complex activities, generally dangerous for workers’ health. Unmanned aerial vehicles (UAVs) can be considered for this purpose, but the absence of data does not permit their use for a quantitative analysis. The main goal of this work is to obtain scientific information for successfully using UAVs in quali-quantitative characterization activities. Materials and methods The influence of the main flight UAV condition parameters on the detection efficiency and minimum detectable activity (MDA) concentration was assessed at lab-scale, considering 241 Am and 152 Eu as simulated soil contaminants. Obtained data were compared with reference to clearance levels. Specifically, the altitude ( h ) and inclination ( θ ) with respect to the soil surface of a small size γ-ray semiconductor CdTe detector and detection time were investigated as flight parameters. h and θ were adopted in the range 0–70 cm and 0°–60°, respectively. Results and discussion Main results reveal that in the case of 241 Am contamination, a duration time of about 13 and 20 min is required for an altitude of 60 and 70 cm, respectively, if an inclination of zero is considered, whereas inclinations higher than 15° lead to much longer times, up to 40 min. In the presence of 152 Eu, results reveal a more marked influence of the variables h and θ on the minimum detection time, with values higher for 241 Am. In terms of MDA, in the case of 241 Am, all the concentration values, with the exception of the highest θ investigated (60°), are below the Italian regulatory limit for altitudes lower than 35 cm and a detection time of 30 min. Higher h up to 50 cm can be considered, reducing the inclination up to 0°, whereas even higher altitudes make the detection of 241 Am not possible. On the other hand, for 152 Eu, the observed MDA values always make the contaminant detection possible. Conclusions All achievements and the calculated fitting parameters are useful preliminary data in the quantitative characterization of soil surface contamination, representing a valuable tool in knowing the soil surface γ-ray activity of 241 Am and 152 Eu for each given detected value. In general, obtained results will allow a better understanding of the technique limits and operating methods required for characterization activities by UAVs with vertical take-off and landing system.