Potential anti-cancer drugs are frequently of low efficacy in clinics due to the lack of predictive models or the insufficient employment of existing preclinical test systems. Three-dimensional (3D) in vitro engineered tumor models can better predict the efficacy of novel drugs by reproducing the in vivo tumor microenvironment. In this study, three sources of scaffolds (decellularized lung scaffold, chitosan/gelatin scaffold, and poly-L-lactic acid scaffold) incorporated with breast cancer cells (MCF-7, 4T1) were bioengineered as a platform to study in vitro solid tumor development The good biocompatibility of three scaffolds favored cell growth and proliferation. Cells in 3D scaffolds were less sensitive to chemotherapy and exhibited characteristics of higher malignancy compared to their 2D counterparts. The expression of breast cancer biomarkers in MCF-7 cells markedly up-regulated in 3D scaffolds in comparison with those in 2D cultures. Cells grown in 3D scaffolds were found to be more tumorigenic and angiogenic in BABL/c mice xenografts than cells grown from monolayers. The results demonstrate that 3D engineered tumor model can better mimic in vivo tumor and can serve as a more appropriate platform for the study and screening of novel cancer therapeutics. (C) 2019 Published by Elsevier B.V.