Successful implementation of disruptive innovation involves numerous challenges, especially for new entrants. This study tries to identify and analyze a set of critical challenges that might plague a new entrant to successfully implement disruptive innovation. Multicriteria decision-making (MCDM) technique of Interpretive Structural Modeling (ISM) was used to analyze the identified challenges, as well as to derive their interrelationship. The study was conducted in the context of the Indian manufacturing sector. The findings revealed that the lack of financial resources, lack of non-financial resources, and lack of top management support emerged as the three key challenges impeding disruptive innovation for manufacturing organizations in India. The motivation–opportunity–ability (MOA) model served as the basic theoretical underpinning for the study. The findings of the study are expected to help managers and policymakers to understand possible challenges associated with the implementation of disruptive innovation, and to develop counter strategies accordingly.