Startups cannot survive and continue their activities without economic profit. And this is achieved through the commercialization of products and services. Commercialization, which has led to the failure and exit of numerous startups, is itself shaped by a set of barriers and drivers. Accordingly, the purpose of this study is to identify the barriers and drivers of commercialization in startups and to analyze their structural relationships using a scientific approach. To achieve this objective, a systematic review of the literature and related scholarly sources was first conducted to identify the factors influencing technology commercialization in startups. These factors were subsequently validated by experts and classified into two categories: barriers and drivers. In the next step, the Interpretive Structural Modeling (ISM) approach was applied to analyze the interrelationships among the components in terms of their influence on one another.The findings indicate that, based on the Driving Forces and dependent forces of the factors, the barrier of “time wastage” was identified as a dependent variable, “technological complexity” emerged as an independent variable, and the remaining barriers and drivers (such as financial resources, risk aversion, skilled human capital, commercialization speed, prototyping, reputation, organizational legitimacy, and networks) were classified as linkage variables. None of the factors were placed in the autonomous category. Furthermore, the results suggest that successful commercialization in startups requires particular attention to more foundational factors such as investment, lack of legitimacy, time wastage, risk aversion, reputation, commercialization speed, and networks.