A structured transdisciplinary method for the experimental determination of friction in the nanometric domain is proposed in this paper. The dependence of nanoscale friction on multiple process parameters on these scales, which comprise normal forces, sliding velocities, and temperature, was studied via the lateral force microscopy approach. The procedure used to characterize the stiffness of the probes used, and especially the influence of adhesion on the obtained results, is thoroughly described. The analyzed thin films were obtained by using either atomic layer or pulsed laser deposition. The developed methodology, based on elaborated design of experiments algorithms, was successfully implemented to concurrently characterize the dependence of nanoscale friction in the multidimensional space defined by the considered process parameters. This enables the establishment of a novel methodology that extends the current state-of-the-art of nanotribological studies, as it allows not only the gathering of experimental data, but also the ability to do so systematically and concurrently for several influencing variables at once. This, in t, creates the basis for determining generalizing correlations of the value of nanoscale friction in any multidimensional experimental space. These developments create the preconditions to eventually extend the available macro- and mesoscale friction models to a true multiscale model that will considerably improve the design, modelling and production of MEMS devices, as well as all precision positioning systems aimed at micro- and nanometric accuracy and precision.