Cutaneous abscesses are the most common skin infections in Amazonia; however, data on the infectious agents in this tropical region are scarce. The humid and hot climate of the Amazon region, coupled with exposure to environmental contaminants from aquatic, telluric, plant, insect, and animal sources, could modify the infectious agents responsible for skin abscesses, which are largely dominated by Staphylococcus aureus (S. aureus) in temperate regions. A retrospective monocentric study was conducted from January 1, 2023 to January 15, 2024. Any patient over 18 years of age admitted to the Surgery Department of Cayenne Hospital, French Guiana, for drained abscesses who had a positive microbiological specimen was included. Contiguous osteoarticular infection, necrotizing fasciitis, amputation, and unfavorable evolution requiring revision surgery were considered complications. Of 123 eligible patients, 118 patients were analyzed. Gram-positive cocci were found in 75% of samples (primarily S. aureus), whereas Gram-negative bacilli were present in 36% of samples. Snakebites accounted for a significant proportion of abscesses (14%; n = 17). In the univariate analysis, infections caused by group 3 Enterobacteriaceae, which naturally produce low-level cephalosporinase (n = 23), Aeromonas hydrophila. (n = 20), and waterborne Enterobacteriaceae (n = 26) were significantly associated with lower limb location, secondary abscess, snakebite, polymicrobial infection, and water exposure. Group 3 Enterobacteriaceae-positive cultures were significantly associated with the occurrence of complications, whereas waterborne Enterobacteriaceae were linked to informal settlement housing. In conclusion, these data indicate that in the Amazon region, empiric antibiotic therapy for infections of the lower limbs or secondary to snakebite should target group 3 Enterobacteriaceae and Aeromonas sp. Sulfamethoxazole-trimethoprim may be an effective treatment option for these patients.