Gastrointestinal malignancies represent a significant public health issue worldwide, characterized by insidious early symptoms and rapid disease progression, posing substantial challenges to clinical diagnosis and treatment. Serum tumor marker testing, with its non-invasive and repeatable dynamic monitoring advantages, has become a core auxiliary tool in the full-cycle management of digestive system tumors. However, single markers detection often suffer from insufficient sensitivity and specificity, leading to potential missed or misdiagnoses and failing to meet the strict requirements of precision medicine. This article aims to systematically elaborate on the core value of combined detection of multiple serum tumor markers detection in the diagnosis and treatment of gastrointestinal malignancies, conducting a deep analysis from multiple dimensions including molecular biological mechanisms, clinical diagnostic efficacy, dynamic monitoring of therapeutic effects, and prognosis assessment. Research indicates that constructing multi-dimensional diagnostic models by scientifically combining markers sensitive to different pathological types can significantly improve the early detection rate, accurately reflect changes in tumor burden, and provide solid evidence-based support for the formulation of individualized treatment plans. This article will explore how the combined detection of multiple indicators can overcome the limitations of single indicators, achieve precise diagnosis through logical complementarity in complex clinical scenarios, and thereby optimize the diagnosis and treatment of gastrointestinal tumors.