Dynamic sub-structuring (DS) has been observed to play a crucial role in dealing with large-scale complex dynamic systems over the years. The broad classes of DS approaches involve coupling of constituent component elements to obtain the response of the assembled system in modal, frequency, and time-domains [1, 2, 3]. The developments of DS approaches in the above mentioned operating domains are quite substantial. However, a comparative assessment for identifying conditions conducive to employ a particular class of DS methods seem to have received less attention in the existing literature both in context of numerical as well as experimental based studies. Therefore, this work will assess the performance of various existing DS approaches in solving structural dynamic systems focusing on real case studies. The importance of the study lies in the identification of a specific operating domain of DS approaches according to the available information on the problem in hand. Moreover, a few case studies will be undertaken to illustrate the effect of uncertainties at the individual component level on the overall system level dynamic response. Although the present study focusses on a numerical investigation, it provides a generalized framework so as to be seamlessly applicable to experimental and/or hybrid analysis.