The extracellular matrix is a fundamental, core component of all tissues and organs, and is essential for the existence of multicellular organisms. From the earliest stages of organism development until death, it regulates and fine-tunes every cellular process in the body. In cancer, the extracellular matrix is altered at the biochemical, biomechanical, architectural and topographical levels, and recent years have seen an exponential increase in the study and recognition of the importance of the matrix in solid tumours. Coupled with the advancement of new technologies to study various elements of the matrix and cell–matrix interactions, we are also beginning to see the deployment of matrix-centric, stromal targeting cancer therapies. This Review touches on many of the facets of matrix biology in solid cancers, including breast, pancreatic and lung cancer, with the aim of highlighting some of the emerging interactions of the matrix and influences that the matrix has on tumour onset, progression and metastatic dissemination, before summarizing the ongoing work in the field aimed at developing therapies to co-target the matrix in cancer and cancer metastasis.