 Collagen is a major component of the tumor microenvironment and plays a key role in cancer fibrosis. It can be regulated by cancer cells through mutations in genes, transcription factors, signaling pathways, and receptors. Furthermore, it can influence tumor cell behavior through integrins, discordant domain receptors, tyrosine kinase receptors, and certain signaling pathways. Additionally, exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression. Other substances in the extracellular matrix such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts also play a role with collagen in cancer immunity and progression. Collagen's structural properties and functions in diverse cancers have been studied extensively, providing insight into its potential use in anti-cancer therapies.