Background: Contamination of medical equipment and the surface environment with bacteria could be the main source of infection in hospital settings. The identification of the main sources of contamination is necessary to overcome this major public health problem, especially in intensive care units and paediatric wards where patients are more susceptible to nosocomial pathogens. Contamination of medical equipment and the surface environment with bacteria could be the main source of infection in high-risk units and wards in hospitals. Objective: The aim of this study was to determine bacterial contamination rate of medical equipment, inanimate surfaces, and indoor air and their drug susceptibility pattern in neonatal intensive care unit and pediatric ward at Hawassa Comprehensive Specialized Hospital, Hawassa city, Southern Ethiopia. Materials and Methods: A hospital-based cross-sectional study with a convenient sampling technique was carried out from 20th October to 30th December, 2020. Samples were collected from medical equipment, inanimate surfaces, and indoor air in neonatal intensive care unit and paediatric ward using aseptic technique. Settle plate method was used to collect indoor air samples. Sample processing and antimicrobial susceptibility testing were done using standard microbiological methods. Data entry and analysis were carried out using SPSS software version 25.0. Results: A total of 229 samples were collected; 56 from medical equipment, 61from inanimate surfaces, and 112 from indoor air. Of the total samples collected 171(74.7%) were culture positive. Thirty-three (58.9%), 26(42.6%), 112(100%) of medical equipment, inanimate surfaces, and indoor air were culture positive respectively. A total of 284 bacteria were identified, out of which 139(48.9%) were Gram-negative and 145(51.1%) Gram-positive. Micrococcus species (41.3%), Acinetobactorer species(13.7%) and by K. pneumoniae(10.2%) were the most commonly isolated bacteria. K. pneumonia were resistant to all antibiotics tested and all S. epidermidus were resistant to 7 antibiotics. Multi-drug resistance was observed in 21.4% of bacteria isolated. Conclusions and Recommendations: In this study, high level of bacterial contamination rate of equipment, inanimate surfaces, and indoor air of neonatal intensive care units and the pediatric wards was found. Multi-drug resistance was detected among most Gram-negative bacteria. Supervision and monitoring of medical equipment, inanimate surfaces, and indoor air at Hawassa University, Comprhensive Specilized Hospital is needed to reduce nosocomial infection.