One of the most common polyoxometalates (POMs) is the Anderson-Evans archetype with the general formula [Hy(XO6)M6O18]n-, where y = 0-6, n = 2-8, M = addenda atoms (MoVI or WVI) and X = a central heteroatom. The Anderson-Evans archetype is a highly flexible POM cluster that allows modification from several point-of-views; i) it can incorporate a large number of different heteroatoms differing in size and oxidation state, ii) it can incorporate inorganic and organic cations and molecules demonstrating different coordination motifs, and iii) covalent attachment with tris(hydroxymethyl)methane ligands allows it to be combined with specific organic functionalities. The catalog of available heteroatoms, counter cations and organic ligands has witnessed a tremendous expansion during the last years ranging from small inorganic anions that act as building-blocks for larger structures to anions in the nanometer range exhibiting multifunctional properties. This in-depth review discusses synthesis approaches and looks into existing Anderson-Evans structures with a special emphasis on structure-property relationship that tris(hydroxymethyl)methane functionalized structures bring. It also covers the successful use of the Anderson-Evans archetype in various fields of classical applications and describes its superiority to other POM archetypes especially in biological applications.