Past research reveals that many lean implementation barriers hinder lean implementation in small and medium-sized enterprises (SMEs). Among many sectors, the manufacturing sector suffers more as it generates more waste while carrying out manufacturing processes. Many manufacturing units make unsuccessful attempts to implement lean principles in their manufacturing systems. Hence, such units must eliminate the prevailing lean barriers to accomplish successful lean implementation. Moreover, the contextual relationship of lean barriers must be studied to understand the effect of such barriers. This paper uses interpretive structural modeling (ISM) to explore lean barriers, their relationships, and their influence on other lean barriers. The present research also reveals the most significant classification of lean barriers into various categories of independent, dependent, autonomous, and linkage using the (MICMAC) Matrice d’Impacts Croisés Multiplication Appliquée á un Classement analysis. ISM and MICMAC together provide relationship modeling and reveal the interrelationship between each lean implementation barrier and its categories, respectively. The ISM model is validated using the Delphi technique. The interpretative ranking process (IRP) is used to rank the barriers. The three significant lean implementation barriers revealed through the IRP include “lack of lean understanding”, “lack of strong quality policy”, and “risk of sustainable practice implementation”. The present research will help practicing managers of SMEs in the manufacturing sector to understand the mutual influence of lean barriers before introducing lean implementation. It is suggested that SMEs work on independent barriers so that dependent barriers can also be overcome with the least amount of resources and effort.