The production of high-quality self-assembled monolayers (SAMs) followed by Llayer-by-Llayer (LbL) self-assembly of macrocycles is essential for nanotechnology applications based on functional surface films. To help interpret of the large amount of data generated by a standard ToF-SIMS measurement, principal component analysis was used. For two examples, the advantages of a combination of ToF-SIMS and PCA for quality control and for the optimization of layer-by-layer self-assembly are shown. The first example investigates how different cleaning methods influence the quality of SAM template formation. The second example focuses on the layer-by-layer self-assembly of macrocycles and the corresponding stepwise surface modification.