Efficient surface cleaning protocols are imperative across diverse industries to ensure product quality and performance. The new direction of nanoelectronics requires surfaces to be cleaned at the nanoscale. In the last decade, surface nanobubbles have been shown to remove nanoparticles from silicon wafers. [1] Nevertheless, the specific surface nanobubble-nanoparticle interaction has not been fully understood, calling for a deeper investigation. We explore the formation and stability of surface nanobubbles by employing atomic force microscopy (AFM). After solvent/water exchange we characterize them in terms of topography and their interaction in different wettability and environment scenarios (i.e., change in solvent, nanoparticle types, gas concentration, and surface functionalization). The presence of NBs can lead to localize changes in wettability, roughness, and chemical reactivity. Managing the balance between enhanced cleaning and surface potential is crucial. Over time, this alteration may impact the substrate’s integrity or alter its performance characteristics. Interestingly, we observe the formation of nanoholes, which we interpret in terms of short ranges forces (DLVO theory) and chemical equilibrium in confinement. The latter takes inspiration from pressure solution as described in geology. It helps identify the physical and chemical interactions occurring when nanoparticle detachment from the substrate. [2] Our research work aims to describe solid-liquid interface, with particular interest to the phenomena correlate the interactions force between surface nanobubble-nanoparticles and surface and nanoparticles-surface. Research on surface nanobubble and the study of their possible application is necessary because there is not a unified vision in the scientific community. The results can impact both the scientific and industrial categories, by addressing respectively unsolved interactions at the nanoscale and upscaling nano-cleaning processes at the macroscale. [1] S. Yang, & A. Duisterwinkel, A. (2011). Removal of Nanoparticles from Plain and Patterned Surfaces Using Nanobubbles. Langmuir, 27(18), 11430– 11435. doi:10.1021/la2010776; [2] K. Kristiansen, M. Valtiner, G.W. Greene, J.R. Boles, J.N. Israelachvili (2011). Pressure solution - The importance of the electrochemical surface potentials. doi:10.1016/j.gca.2011.09.019