This review focused on the impact of F18+ E. coli on pig production and explored nutritional interventions to mitigate its deleterious effects. F18+ E. coli is a primary cause of PWD in nursery pigs, resulting in substantial economic losses through diminished feed efficiency, morbidity, and mortality. In summary, the F18+ E. coli induces intestinal inflammation with elevated IL6 (60%), IL8 (43%), and TNF-α (28%), disrupting the microbiota and resulting in 14% villus height reduction. Besides the mortality, the compromised intestinal health results in a 20% G:F decrease and a 10% ADFI reduction, ultimately culminating in a 28% ADG decrease. Among nutritional interventions to counter F18+ E. coli impacts, zinc glycinate lowered TNF-α (26%) and protein carbonyl (45%) in jejunal mucosa, resulting in a 39% ADG increase. Lactic acid bacteria reduced TNF-α (36%), increasing 51% ADG, whereas Bacillus spp. reduced IL6 (27%), increasing BW (12%). Lactobacillus postbiotic increased BW (14%) and the diversity of beneficial bacteria. Phytobiotics reduced TNF-α (23%) and IL6 (21%), enhancing feed efficiency (37%). Additional interventions, including low crude protein formulation, antibacterial minerals, prebiotics, and organic acids, can be effectively used to combat F18+ E. coli infection. These findings collectively underscore a range of effective strategies for managing the challenges posed by F18+ E. coli in pig production.