Background/Objectives: Antimicrobial resistance (AMR) poses a global threat, exacerbated by the overuse and misuse of antimicrobials. This study evaluated antimicrobial use and prescribing patterns among inpatients in three tertiary hospitals in Nepal. Methods: A cross-sectional point prevalence survey of the inpatient module of the standardized Global-PPS methodology was conducted across three tertiary hospitals in Nepal during the 2022 Global-PPS Period 2 (P2) survey, carried out between May and August 2022. Data were collected via a paper-based form (University of Antwerp;) and analyzed descriptively. Antimicrobial use was defined as the proportion of inpatients receiving at least one systemic antimicrobial on the day of the survey. Results: Of 379 patients eligible for the study, 233 (61.5%) received at least one antimicrobial, with the highest prevalence observed in adult and neonatal intensive care units (ICUs). Out of 371 antibiotic prescriptions, third-generation cephalosporins (30.2%) and carbapenems (8.1%) were the most frequently prescribed, and 61.0% of overall antibiotics belonged to the Watch group of WHO AWaRe classification. Surgical prophylaxis often exceeded recommended durations, with 91.5% of prophylactic antibiotics prescribed for more than one day. Empirical therapy dominated 56.33% of all prescriptions, with targeted therapy limited to 4.04%. Conclusions: The high overall prevalence of antimicrobial use, the reliance on empirical therapy, and over-reliance on Watch-group antibiotics and Unclassified AWaRe antibiotics highlights the urgent need for robust antimicrobial stewardship programs in Nepal.