Objective Chemotherapy medications are usually having high costs, and new targeted drugs can be especially expensive, representing a challenge on healthcare, particularly in low- and middle-income countries. As cytotoxic leftover management is crucial for reducing medication wastage, the aim of this study is to evaluate and optimize leftover management circuit in NIO’S Pharmacy Centralized Chemotherapy Preparation Unit (CCPU) through a Failure Mode, Effects and Criticality Analysis (FMECA), and propose continuous improvement element to enhance the security of the process. Method The FMECA were conducted in NIO’s CCPU from March to May 2023, then continuous improvement plan was established to enhance the security of the process. The failure modes, their causes, impact, and criticality were assessed through criticality index calculation (CI = severity × frequency × detectability), and the risk concerned safety and effectiveness disruptions in chemotherapy preparation circuit using cytotoxic leftover. Results Leftover management circuits were described in flowchart form, where 18 failure modes were detected in four different steps of the process from chemotherapy preparation to disposal. Failure with highest critical index were detected in the case of equipment malfunction, improper storage temperature, and humidity. Continuous improvement recommendations were proposed in a table form. Conclusion FMECA analysis applied to NIO’s chemotherapy leftover management process allowed us to evaluate, secure, and optimize the circuit, and to propose several actions to implement in a perspective of continuous improvement.