Circulatory system proteins play a central role in human physiology; therefore, profiling plasma proteins has been explored widely as a robust and dynamic tool in studying diseases. Here, we investigated the proteomic profile of plasma in 1,118 pan-cancer patients. The integrative analysis uncovered diverse molecular characteristics of different cancer types and bridged the plausible connection with the clinical features, including tumor stages. The findings demonstrate that the balance between lipid and glucose metabolisms is important in regulating immune infiltration. The pre- and post-surgery comparison of the plasma proteome indicated that tumor-induced angiogenesis is overexpressed in the tumor, and the differences between the proteome patterns could monitor post-surgery therapeutic effects. Finally, we developed a panel of tumor-type-specific proteins to classify tumor types with >95% sensitivity/specificity. Collectively, this study portrayed the plasma proteome landscape of human cancers and screened reliable biomarkers that could assist in diagnostic and drug discovery efforts.