<p>The application of decellularized extracellular matrix from cultured cells to tissue has increasingly emerged as a valuable tool in cancer research. To discover and explore personalized therapeutic options, the screening of drugs in the 3D in vitro conditions using ECM is highly essential, which mimics similar in vivo physiological conditions for the drug discovery process. However, constant remodelling or evolving tumour microenvironment, is one of the major reasons for the tumour heterogeneity among individuals which serves as the major challenge to be addressed for the treatment strategies. Thus, the in-depth understanding of the extracellular matrix (ECM) of tumour microenvironment is much crucial for bringing out new therapeutic interventions. Hence this review sheds light on the extracellular matrix components, alterations and its role in the tumour microenvironment for tumour progression and metastasis. Also, this review, discussed about different xenograft tissue-derived ECM and in vitro cell culture derived decellularized ECM for various in vitro 3D culture models to understand various biological mechanisms including proliferation, migration, invasion and chemo resistivity of the cancer cells against the therapeutic molecules for cancer therapy applications.</p>