Maize (Zea mays L.) breeders are concerned about the narrowing of the genetic base of elite germplasm. To reverse this trend, elite germplasm from other geographic regions can be introgressed, but due to lack of adaptation it is difficult to assess their breeding potential in the targeted environment. The objectives of this study were to (1) investigate the relationship between European and US maize germplasm, (2) examine the suitability of different mega-environments and measures of performance to assess the breeding potential of exotics, and (3) study the relationship of genetic distance with mid-parent heterosis (MPH). Eight European inbreds from the Dent and Flint heterotic groups, 11 US inbreds belonging to Stiff Stalk (SS), non-Stiff Stalk (NSS), and CIMMYT Pool 41, and their 88 factorial crosses in F(1) and F(2) generations were evaluated for grain yield and dry matter concentration. The experiments were conducted in three mega-environments: Central Europe (target mega-environment), US Cornbelt (mega-environment where donor lines were developed), and Southeast Europe (an intermediate mega-environment). The inbreds were also fingerprinted with 266 SSR markers. Suitable criteria to identify promising exotic germplasm were F(1) hybrid performance in the targeted mega-environment and F(1) and parental performance in the intermediate mega-environment. Marker-based genetic distances reflected relatedness among the inbreds, but showed no association with MPH. Based on genetic distance, MPH, and F(1) performance, we suggest to introgress SS germplasm into European Dents and NSS into European Flints, in order to exploit the specific adaptation of European flint germplasm and the excellent combining ability of US germplasm in European maize breeding programs.