In vitro tumour models utilise various cancer cells and an appropriate extracellular matrix equivalent to recapitulate the in vivo tumour microenvironment. Three-dimensional tissue surrogates (e.g., decellularised tissue grafts, decellularised monolayers, hydrogels, electrospun fibres and sponges) are increasingly used as alternatives to conventional two-dimensional monolayer cultures to model the tissue environment more faithfully for drug development and screening. Herein, we critically assess the advances and shortfalls of these three-dimensional systems as in vitro models of cancer.