Introduction: Antimicrobial resistance (AMR) is a serious and sensitive threats to human and animal health issue from successive decades of rapidly rises that has develop several antibiotics access from modern medicine ineffective in response to common infections. Prevalent application of antimicrobials in agriculture, improper disposal of antimicrobials, and waste-water discharges from pharmaceutical manufacturing sites, health facilities, farms, and slaughterhouses distributed resistant pathogens into the environment. Several problems are associated through AMR within reduces the effectiveness of treatment, increases the costs of health care, jeopardizes health-care gains to society, risk of death, threatens health security, and damages trade and economies. Aims: Nepal requires a National Action Plan (NAP) to control and regulate the issue of AMR via a __ampersandsignlsquo;One Health__ampersandsignrsquo; approach within the increasing burden of AMR and Antimicrobial Resistance Genes (ARGs). Methods: According to current evaluation report, in 2019, 1.27 million deaths were directly concerned to medicine resistant infections globally which was projected by the WHO and UN. Results: Several actions i.e. AMR stewardship, AMR surveillance, AMR awareness programme, management of several environmental drivers (i.e., antimicrobials, pharmaceuticals wastes, biocides, metals, micro plastics, potentially toxic substances, etc.) are undertaken to regulate the risk of AMR by the Government of Nepal within different strategies via different hospitals and laboratories and the reports are estimated by the different regulatory bodies i.e., Global Action Plan (GAP), NAP, DDA, Global Antimicrobial Resistance Surveillance System (GLASS), National health policy, National Drug Policy and others. Conclusion: All the people have to be wisely understand about the application of scientific approach to assessment of AMR and ARGs regarding environmental drivers which are extremely future threats to the human, animal and environmental health.