Biological invasions are a major threat to natural ecosystems and agroecosystems, while weed flora is noticeably changing globally. In this study we evaluated the potential of cut-leaf ground-cherry (Physalis angulata L.), a species native to America, to invade the semi-arid regions of Greece. Greenhouse and laboratory experiments were conducted to evaluate the effects of different environmental resources (nutrient and water availability) on seedling growth, biomass production, fecundity, and seed germination of four populations of cut-leaf ground-cherry. Our results suggest that cut-leaf ground-cherry does not tolerate extreme drought during the first growth stages, while it can survive and produce adequate and rapidly germinated seed (> 85%) under low soil moisture conditions. Moreover, high water and nutrient availability results in high growth and biomass production and ensures high seed production, reaching more than 4000 seeds plant-1. We suggest that soil water content and nutrient availability are the two critical factors affecting the invasive potential of cut-leaf ground-cherry in semi-arid environments. Understanding the plant’s ecological features through a study conducted at an early stage rather than a late stage of invasion will help us to take appropriate control measures for this species, which should primarily target frequently fertilized fields after precipitation events.