Background/Objectives: Antimicrobial resistance (AMR) is a critical global health threat, leading to increased morbidity, mortality, and healthcare costs. This study aimed to identify the most common bacterial pathogens and their resistance profiles from 2179 positive clinical cultures from inpatients at “Victor Babes” Hospital of Infectious Disease and Pneumoftiziology Timisoara in 2023. Methods: Samples were collected from sputum, bronchial aspiration, hemoculture, urine, wound secretions, catheter samples, and other clinical specimens. Results: Key pathogens identified included Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, with notable resistance patterns, observed K. pneumoniae exhibited high resistance rates, notably 41.41% in Quarter 1, while E. coli showed 35.93% resistance in the same period. S. aureus, particularly MRSA, remained a persistent challenge, with 169 cases recorded over the year. A. baumannii and P. aeruginosa displayed alarming levels of multi-drug resistance, especially in Quarter 3 (88.24% and 22.02%, respectively). Although there was a general decline in resistance rates by Quarter 4, critical pathogens such as S. aureus and K. pneumoniae continued to exhibit significant resistance (81.25% and 21.74%, respectively). Conclusions: The study’s findings align with the broader antimicrobial resistance trends observed in Romania, where high resistance rates in K. pneumoniae, E. coli, S. aureus (MRSA), Acinetobacter, and Pseudomonas species have been widely reported, reflecting the country’s ongoing struggle with multi-drug-resistant infections. Despite some reductions in resistance rates across quarters, the persistent presence of these resistant strains underscores the critical need for strengthened antimicrobial stewardship, infection control measures, and continuous surveillance to combat the growing threat of AMR in Romania and similar healthcare settings.