Background: Clinical decision support (CDS) functionalities in Computerized Provider Order Entry system (CPOE) need to be identified by the institutional healthcare providers in developing countries. In this regard, CDS functionalities should be a priority for the execution in CPOE. Objectives: Thus, our study was done to identify and prioritize the CDS functionalities in CPOE. Methods: A Two-round Modified Delphi process was used. Firstly, a systematic search was conducted in electronic databases from the date of database inception to February 2019 for identifying CDS functionalities integrated into CPOE. Studies were retrieved from databases, including PubMed, Embase, ProQuest, Scopus, Web of Science, Cochrane, Science Direct, ACM digital library, and IEEE Xplore Digital Library. Secondly, the Modified Delphi method was carried out in 2019 to provide contextual priorities regarding CDS functionalities in CPOE in two iterative rounds. A total of 12 experts working in the three Intensive Care Units (ICUs) with more than three years of experience with homegrown CPOE in Shiraz Nemazee Teaching Hospital, including two clinical pharmacists, two health information management faculty member, four cases with critical care fellowship, and four critical care experts participated in the study. The ≥ 66.6% agreement was considered as the consensus level. SPSS software version 24 was used for statistical analysis. Results: Totally, 327 studies, which met eligibility criteria were found. A number of 60 potential CDS functionalities in CPOE were identified from eligible studies. Also, 13 out of 60 CDS functionalities reached high priority consensus after 2 iterative Delphi rounds, including drug-allergy checking (83.3%), basic dosing guidance (75%), single dosing checking (66.7%), duplicate therapy checking (66.7%), drug-pregnancy alerts (75%), time-based alerts (66.7%), alert for deep vein thrombosis prophylaxis (66.7%), alerts for duplicate medication order checking (66.7%), drug-drug interaction checking (75%), intelligent dosing guidance based on the patients’ characteristics (66.7%), renal-drug problems checking (83.3%), drug-disease interaction checking (66.7%), and displaying medication/test cost (75%). Conclusions: Our study identified high-priority CDS functionalities to be considered in the CPOE system from the viewpoint of multidisciplinary experts, especially in Iran. Results of this study may be beneficial to plan, design, and implement CDS functionalities in CPOE in the ICU.