The generation of biomedical waste (BMW) in hospitals presents a significant hazard to both healthcare workers (HCWs) and the environment. The management of BMW is a challenge regarding inappropriate behavior among HCWs, leading to improper segregation of the BMW, which deserves attention.The indiscriminate BMW management issue in India has attracted the attention of the highest judicial bodies. The rise in the incidence of needle stick injuries is a severe threat to waste handlers and is mainly due to improper segregation practices. This study aimed to identify the challenges in BMW management in the institute and develop a strategy to improve the knowledge and practices of healthcare professionals (HCPs) in BMW management. A process-based intervention was developed and implemented that involved facility inspection rounds, focused group discussions with HCWs, preparation of information, education, and communication (IEC) materials, signage, staff training, and improved infrastructure and supplies for waste collection. A questionnaire-based evaluation of the staff's knowledge of BMW management was conducted, and the impact of the intervention was assessed from the hospital infection control audit reports. Multiple reasons for poor compliance with BMW segregation practices were identified, and it improved from 57% to 91% with interventions. A significant difference was noted in the knowledge level of staff before and after the interventions.Post-intervention score was highest among the nurses (98.5%), followed by sanitation staff (92.7%), doctors (89.25%), and paramedics (81.7%). Incorrect segregation practices of BMW and incidents of occupational exposure to blood and body fluids are reduced with interventions in the study. Robust supply chain management with regular training of staff is vital to ensure compliance in BMW management.