Background: Regarding the growing burden of non-communicable diseases (NCDs) and exposure to their risk factors, and the continuous need for nationwide data, we aimed to develop the latest round of the STEPwise Approach to NCD Risk Factor Surveillance (STEPS) survey in 2021 in Iran, while the COVID-19 pandemic was still present. Methods: In addition to the three main steps of this survey, including questionnaires, physical measurements, and laboratory assessments, we adapted the survey with the situation caused by the COVID-19 pandemic, by adding to various aspects of study phases and changing some scientific and executive procedures in this round of STEPS survey in Iran. These changes were beyond the initial novelties embedded within the survey before the pandemic, by refining the study protocol benefiting from the previous experiences of the STEPS survey. Results: By amending the required changes, we could include a total of 27874 individuals in the first step of the survey. This number was 27745 and 18119 for the second and third steps. Comparing the preliminary results with the previous nationwide surveys, this study was highly representative on both national and provincial levels. Also, implementing the COVID-19 prevention and control strategies in all stages of survey led to the least infection transmission between the study investigators and participants. Conclusion: The novel initiatives and developed strategies in this round of Iran STEPS survey provide a state-of-the-art protocol for national surveys in the presence of an overwhelming catastrophe like the COVID-19 pandemic and the triggered limitations and shortages of resources.