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Intra-abdominal infections encompass a range of medical conditions categorized by their complexity. Uncomplicated infections involve inflammation or infection limited to a single abdominal organ, such as acute appendicitis or cholecystitis, without extending to the peritoneum, while complicated infections spread to the peritoneal cavity. The key associated microbiological agents include Gram-positive cocci, Gram-negative Enterobacteriaceae, and obligate anaerobes, with common pathogens being Escherichia coli, Klebsiella pneumoniae, Streptococcus species, and Bacteroides fragilis. Treatment options include well-established antibiotics and newer agents like meropenem, metronidazole, and ceftazidime/avibactam. Meropenem, a carbapenem antibiotic, is known for its broad-spectrum efficacy and low toxicity, making it suitable for severe infections. Ceftazidime, a third-generation cephalosporin, is effective against Pseudomonas aeruginosa, especially when paired with avibactam, a β-lactamase inhibitor, enhancing its effectiveness. Metronidazole disrupts bacterial DNA, targeting anaerobic bacteria and protozoa. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of the ceftazidime-avibactam plus metronidazole combination compared to meropenem for intra-abdominal infections. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a comprehensive search of databases such as PubMed, Web of Science, and the Cochrane Library was conducted. Results showed that the combination therapy had a slightly higher overall adverse event rate (5.57%) compared to meropenem (4.56%), although this difference was not statistically significant [risk ratio (RR): 1.22; 95% confidence interval (CI): 0.78-1.93; p = 0.39]. Meropenem demonstrated a significantly higher clinical response rate in ceftazidime-susceptible infections (89.93% vs. 85.88%; RR: 0.96; 95% CI: 0.93-0.99; p = 0.009). No significant differences were observed in ceftazidime-resistant infections. Overall, the findings suggest that ceftazidime-avibactam combined with metronidazole is a viable alternative to meropenem, highlighting the need for further research to optimize treatment strategies amid rising antibiotic resistance.