This study reproduces the complex relationships between tumour plasma cells and their bone marrow microenvironment in multiple myeloma in vitro. These relationships are established both with other cells and with the extracellular matrix and are key factors in tumour progression, generating resistance to antitumour drugs in the cellular and non-cellular environments. This paper proposes a 3D microenvironment model designed to capture the main components of the multiple myeloma tumour microenvironment. Multiple myeloma cells (MMCs) were dispersed in a microgel medium formed by gel-textured microspheres. The proteins and polysaccharides considered important in the interaction of the MMCs with their non-cellular environment were successfully grafted onto the surface of the microspheres, while human mesenchymal stem cells (MSCs) were cultured in a pellet with non-functionalised microspheres. The MSCs pellet was placed in the well plate together with the microgel and the MMCs and orbitally shaken to maintain them in suspension. The viability, cell cycle and proliferation of the RPMI8226, MM1S and U266 multiple myeloma cell lines and the direct adhesion of MMCs to the MSC pellet were quantified. The results revealed that all three cell lines are able to grow satisfactorily. In addition, the normal behaviour of the MMCs is not modified in any of the culture conditions studied.