Infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) and multidrug-resistant P. aeruginosa (MDR-PA) pose major therapeutic challenges. The limited availability of new antibiotics necessitates evaluating rational combination therapies. This study aimed to compare the in vitro efficacy of meropenem versus meropenem-amikacin combination against carbapenem-resistant P. aeruginosa isolates (including CRPA and MDR-PA). An in vitro experimental study using the checkerboard method was performed on 10 clinical isolates (3 CRPA and 7 MDR-PA) obtained from Dr. Soetomo General Hospital, Surabaya (June-October 2025). Three isolates that showed a decrease in meropenem Minimum Inhibitory Concentration (MIC) to the susceptible range upon confirmatory testing were excluded from the combination synergy analysis. The effectiveness of the combination was evaluated by comparing the MIC of meropenem with that of the combination. Antibiotic interactions were analyzed using the Fractional Inhibitory Concentration Index. Data were analyzed using the Mann-Whitney U test, with the primary analysis focusing on the combined group of resistant isolates. The median MIC of meropenem for the combined CRPA and MDR-PA isolates was 32 µg/mL. The checkerboard test revealed an additive interaction as the dominant effect (71.4%), followed by synergistic (14.3%) and indifferent (14.3%) effects. No antagonistic effects were observed. Statistical analysis of the combined group showed that the meropenem-amikacin combination was significantly more effective in reducing the MIC compared to monodrug (median MIC combination: 4 µg/mL vs. monodrug: 32 µg/mL; P = 0.009). These findings support the consideration of this combination as a therapeutic option for such infections.