Simple Summary: The modern intensive practices in pig production to enhance productivity have increased post-weaning diarrhea (PWD), often caused by F18(+) Escherichia coli. Antibiotics have been widely used in animal production to improve growth; however, their overuse has led to antibiotic-resistant bacterial pathogens, posing risks to both the sustainability of pig production and public health. The pathogenesis of F18(+) E. coli damages the intestinal morphology, barrier function, microbiota composition, and immune responses in nursery pigs, leading to reduced growth performance. Various nutritional interventions have been investigated to combat the PWD issue, including low crude protein formulation, antibacterial minerals, probiotics, prebiotics, postbiotics, and phytobiotics, aiming to enhance intestinal microbial composition, health, and growth performance. Implementing effective strategies to control F18(+) E. coli is crucial for pig production. Therefore, this review is to explore the impact of F18(+) Escherichia coli on pig production, particularly its association with post-weaning diarrhea (PWD) in nursery pigs, and the nutritional strategies to counter its harmful effects. 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-alpha (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-alpha (26%) and protein carbonyl (45%) in jejunal mucosa, resulting in a 39% ADG increase. Lactic acid bacteria reduced TNF-alpha (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-alpha (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.