Background: Morganella morganii, once regarded as a benign intestinal commensal, now poses a serious threat due to its intrinsic AmpC β-lactamase production and increasing multidrug resistance. Objective: This study aimed to assess the efficacy of antibiotic combination therapies against MDR Morganella morganii isolates, specifically evaluating ceftazidime plus amikacin and amikacin plus imipenem regimens to improve treatment outcomes. Methods: A cross-sectional observational and experimental study was conducted from November 2022 to June 2023 at Dhaka Medical College Hospital, Bangladesh. Seven clinical Morganella morganii strains were isolated from urine, wound, blood, and stool samples. Identification was performed using culture, biochemical tests, and PCR. Antimicrobial susceptibility was determined by disc diffusion and MIC via agar dilution following CLSI (2022) guidelines using standard protocols. Results: Seven isolates of Morganella morganii were recovered, representing an overall prevalence of 1.72%. Urine samples yielded 42.85% of isolates, while wound samples contributed 28.57%. Males accounted for 71.42% of cases, predominantly in the 26–35-year age group. ESBL production was observed in 28.57% of isolates, with PCR confirming bla_CTX-M and bla_TEM genes in 50% each among ESBL-positive strains. Carbapenemase production was detected in 50% and 25% of imipenem-resistant isolates by CD assay and DDS test, respectively. Overall, 57.14% were MDR and 14.28% XDR. Detailed calculations indicate significant associations between risk factors and resistance patterns with high significance. Conclusion: This study underscores the urgent need for early detection and targeted combination therapy to combat MDR and XDR Morganella morganii, with ceftazidime-amikacin and amikacin-imipenem regimens showing promising clinical potential.