Background/Objectives: This study aimed to evaluate the chemical composition and antimicrobial activity of Cordia verbenacea essential oil (EOCV) and to develop and characterize a gel-based nanoemulsion of C. verbenacea essential oil (NECV). Methods: The EOCV was chemically characterized by gas chromatography (GC-FID and GC-MS). The nanoemulsion was prepared using EOCV, the surfactants Cremophor and Plurol Oleique, and phosphate buffer at pH 5.5, and was subjected to experiments to determine its stability, irritant potential and in vitro skin permeation. Results: The main chemical compounds identified in EOCV were α-pinene (33.05%) and β-caryophyllene (25.11%). The EOCV exhibited antimicrobial activity with MIC and MBC values ranging from 6.3 to 25.0 µL/mL for the yeasts Candida albicans and C. krusei, 11.3 to 25.0 µL/mL for the Gram-positive bacteria Bacillus cereus, Staphylococcus aureus, and Enterococcus faecalis, and 12.5 to 75.0 µL/mL for the Gram-negative bacteria Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. The NECV showed a droplet size of 126.80 nm, a polydispersity index (PDI) of 0.49, a zeta potential of −18.50 mV and a pH of 5.3 and remained stable for 60 days of storage at 25 °C and 4 °C. The HET-CAM irritation test showed that the formulation is non-irritating. The in vitro skin permeation assay showed that the NECV penetrated the deeper layers of the skin, demonstrating its ability to overcome the Stratum corneum barrier. Conclusions: These results are highly promising regarding the potential use of NECV for topical application for the treatment of infected skin wounds.