Clinical decision support systems (CDSSs) provides vital information for managing patients by advising clinicians through an alert or reminders about adverse events and medication errors. Clinicians receive a high number of alerts, resulting in alert override and workflow disruptions. A systematic review was carried out to identify factors affecting CDSS alert appropriateness in supporting clinical workflows using a recently introduced framework. The review findings identified several influencing factors of CDSS alert appropriateness including: technology (usability, alert presentation, workload and data entry), human (training, knowledge and skills, attitude and behavior), organization (rules and regulation, privacy and security) and process (waste, delay, tuning and optimization). The findings can be used to guide the design of CDSS alert and minimise potential safety hazards associated with CDSS use.