This review article considers the following aspects: naturally distributed chemical elements and their enrichments, and the increased occurrence of PTEs due to anthropogenic and urban activities, as well as due to the geochemical uniqueness of certain geochemical landscapes, depending on the lithological environment. The review article is the result of many years of successful cooperation between the Geological Survey of Slovenia and the Faculty of Natural Sciences in Skopje, Ss. Cyril and Methodius University in Skopje, as well as several other institutions from North Macedonia, Russia and Romania but, also, through the voluntary and enthusiastic work of Prof. Trajče Stafilov’s PhD and Master’s students. To create the Geochemical Atlas, the territory of North Macedonia was covered with 995 sampling locations, but 16 separate areas with soil contamination were additionally sampled. The total sum of all collected soil samples was 3983 from 2449 different sampling sites in the period from 2006 to 2017. The analyses were performed at the Institute of Chemistry, Faculty of Natural Sciences in Skopje, at the Ss. Cyril and Methodius University in Skopje, North Macedonia, at the Research Institute for Analytical Instrumentation (ICIA), Cluj-Napoca, Romania, at the Joint Institute for Nuclear Research in Dubna, Moscow Region, Russia, and at Acme Labs in Vancouver, Canada. The sum of all analysed soil samples in all four mentioned laboratories was 7991 from 2006 to 2017. Using advanced mathematical methods such as multivariate statistical methods (HCA, FA, PCA) and artificial neural networks–multilayer perceptron (ANN-MP), predictions were made about the concentrations of potentially toxic elements (PTEs) and their distribution in real space. In less than two decades (2007–2023) of fruitful collaboration, a large number of scientific works have been published: 188 scientific publications, 8 geochemical atlases and 23 chapters in monographs.