Single-electron devices operating at room temperature require sub-5 nm quantum dots having tunnel junctions of comparable dimensions. Further development in nanoelectronics depends on the capability to generate mesoscopic structures and interfacing these with complementary metal–oxide–semiconductor devices in a single system. The authors employ a combination of two novel methods of fabricating room temperature silicon single-electron transistors (SETs), Fowler–Nordheim scanning probe lithography (F-N SPL) with active cantilevers and cryogenic reactive ion etching followed by pattern-dependent oxidation. The F-N SPL employs a low energy electron exposure of 5–10 nm thick high-resolution molecular resist (Calixarene) resulting in single nanodigit lithographic performance [Rangelow et al., Proc. SPIE 7637, 76370V (2010)]. The followed step of pattern transfer into silicon becomes very challenging because of the extremely low resist thickness, which limits the etching depth. The authors developed a computer simulation code to simulate the reactive ion etching at cryogenic temperatures (−120 °C). In this article, the authors present the alliance of all these technologies used for the manufacturing of SETs capable to operate at room temperatures.