This case report describes the unusual presentation of a 32-year-old male from Guayaquil, Ecuador, who was diagnosed with a rare triple infection caused by Salmonella typhi, Leptospira, and Campylobacter coli. The patient presented with persistent high fever, severe gastrointestinal symptoms, abdominal pain, and jaundice, following the consumption of street food in a resource-limited area. Important clinical findings included hepatosplenomegaly and elevated liver enzymes, which initially complicated the differential diagnosis. Laboratory tests confirmed the presence of all three pathogens, presenting significant diagnostic and therapeutic challenges due to overlapping symptoms and potential antimicrobial resistance (AMR).The main diagnoses included typhoid fever, leptospirosis, and campylobacteriosis, each requiring distinct yet coordinated treatment approaches. The patient was managed with a combination of antibiotics targeting each pathogen and supportive care to address dehydration and liver dysfunction. After a prolonged hospital stay, the patient recovered with no residual symptoms, underscoring the success of a tailored, multidisciplinary approach in the context of limited healthcare resources. This case underscores the importance of clinical awareness regarding co-infections, particularly in areas with inadequate sanitation, where infectious diseases are endemic. The successful management of this complex case highlights the necessity of rapid, accurate diagnostics and coordinated therapeutic strategies to improve outcomes in patients with multi-pathogen infections. This report also emphasizes the critical need for surveillance and tailored interventions in regions facing rising AMR, enhancing our understanding of how to approach emerging infectious diseases in underserved populations.