The increasing threat of multidrug-resistant (MDR) bacterial infections has significantly undermined the efficacy of conventional antibiotics, prompting the need for novel therapeutic strategies. This study explores the synergistic antimicrobial potential of selected essential oils in combination with standard antibiotics against clinically relevant MDR pathogens, including Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Essential oils such as clove, oregano, cinnamon, and thyme were evaluated alongside antibiotics like ampicillin, ciprofloxacin, and tetracycline using standard in vitro assays. The study assessed minimum inhibitory concentrations (MICs), calculated fractional inhibitory concentration indices (FICI), and evaluated biofilm inhibition and efflux pump modulation. Results showed that the combined treatments significantly reduced MIC values and exhibited strong synergistic effects (FICI ≤ 0.5) in most cases. The combinations also enhanced biofilm disruption and efflux pump inhibition compared to individual agents. These findings suggest that essential oils, when paired with antibiotics, offer a promising approach to combat antibiotic resistance and improve infection management.