The tumour microenvironment (TME), in particular the extracellular matrix (ECM) has been increasingly linked to the tumour aggressiveness and invasion. The dynamic interplay between cells and ECM regulates the normal function of tissues, modulating the cellular behaviour and activating signalling events, mainly triggered by the well-structured and organized components of the ECM. In cancer, the changes on the ECM composition derived from the deregulation of production and degradation of its constituents, alters the biochemical (ex. upregulation of metalloproteinases, deposition of proteins) and mechanical (crosslinking extension of the matrix) features of the extracellular space, changing the normal function of tissues. From this perspective, the engineering of 3D models that mimics the TME, allowing the in-vitro study of cancer cells behaviour, has emerged. These 3D models have been used to screen the role of the ECM components, such, proteins and glycans on cancer cells’ behaviour. Moreover, the development of 3D TME models allows the recreation of the ECM by tuning its porosity and density, enabling the exchanges of nutrients, oxygen and biochemical factors, which are essential for cell adhesion, proliferation and migration. In the following chapter it will be reviewed the natural-based materials used for the construction of these 3D models, such as collagen, hyaluronic acid, fibronectin or laminin, components of the ECM, alginate and chitosan. In addition, the use of synthetic-based materials such PEG, PLA or PLGA, that has been widely used in the development of 3D cancer models due to their biocompatibility and the ability to easily tune its physical properties, will be also briefly reviewed.