Cancer is a complex disease in which tumor cells are surrounded by a dynamic tumor microenvironment (TME) composed of other cell types (cancer-associated fibroblasts, mesenchymal stem cells, immune and vascular cells, among others) and a matrix that greatly affect tumor development and progression. The growing need for in vitro models that mimic these features of native tumors has led to the development of 3D models with decellularized extracellularized matrices (dECMs) as an alternative to conventional 2D models. These dECMs offer a more accurate representation of TME components and are an alternative to conventionally employed matrices for the culture of patient-derived organoids, structures that show parallel sensitivity and resistance to patients and are very good platforms for pharmacological studies. In general, these new 3D models may lead to better results in the research of new cancer treatments. In this project, we focus on CART therapy, which may have limitations in the treatment of solid tumors with a very dense extracellular matrix, as this hinders the penetration of immune cells and reduces their efficacy. Thanks to these 3D models based on dECMs that incorporate the tumor microenvironment, it is possible to simulate these barriers and evaluate the efficacy of CART therapy in a more physiological context. This will help us to identify possible limitations and design strategies to overcome them, thus improving the clinical success of these advanced therapies.