Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine with roles in the central nervous system (CNS) and gastrointestinal function. Recent research has established a strong association between serotonergic components and carcinogenic mechanisms, highlighting its dual role in tumourigenesis and immunomodulation. This review provides an overview of 5-HT's biosynthesis, metabolism, and functional modes, emphasizing its immunomodulatory activities in human cancers. Serotonin's mitogenic properties have led to the repurposing of serotonergic-targeted drugs for cancer therapy. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonin receptor-directed therapy, including agonists and antagonists, shows promising clinical options. Selective serotonin reuptake inhibitors (SSRIs) also exhibit antitumour effects, particularly in breast cancer and colorectal cancer. However, the functions of serotonin in cancer pathogenesis remain complex and contradictory, influenced by tissue-specific distribution and serotonergic signalling diversity. Understanding these mechanisms is crucial for developing effective therapeutic strategies targeting serotonin pathways in cancer treatment.Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine with roles in the central nervous system (CNS) and gastrointestinal function. Recent research has established a strong association between serotonergic components and carcinogenic mechanisms, highlighting its dual role in tumourigenesis and immunomodulation. This review provides an overview of 5-HT's biosynthesis, metabolism, and functional modes, emphasizing its immunomodulatory activities in human cancers. Serotonin's mitogenic properties have led to the repurposing of serotonergic-targeted drugs for cancer therapy. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonin receptor-directed therapy, including agonists and antagonists, shows promising clinical options. Selective serotonin reuptake inhibitors (SSRIs) also exhibit antitumour effects, particularly in breast cancer and colorectal cancer. However, the functions of serotonin in cancer pathogenesis remain complex and contradictory, influenced by tissue-specific distribution and serotonergic signalling diversity. Understanding these mechanisms is crucial for developing effective therapeutic strategies targeting serotonin pathways in cancer treatment.