BOLD-100 (sodium trans-[tetrachlorobis (1H-indazole)ruthenate(III)]) is a clinical stage anticancer drug candidate that targets GRP78 and impacts the ER stress responses in cancer cells. Despite expanding knowledge about its multimodal mechanism of action from preclinical studies, little is known about the metabolic effects of BOLD-100 effects in patients. This study is an exploratory analysis of the blood plasma from a subset of metastatic colorectal carcinoma (mCRC) patients who were participants in a Phase 1b/2a dose escalation study (NCT04421820) using a multi-omic strategy, based on proteomic and fatty acid/oxylipin analysis. BOLD-100 treatment was found to exhibit systemic, dose-dependent effects that were more pronounced on the fatty acid/oxylipin level compared to the protein level. The dose-dependent effects were characterized by increased abundances of multiple pro-inflammatory and -resolving mediators. Those were paralleled by increased APOC1 and decreased CD5L abundances, which may represent a physiological response to the liberated fatty acids and oxylipins. Altered abundances of CDF and APOC2-3 indicate further lipid crosstalk between adipocytes and lipoproteins from the liver, respectively. Finally, a potential prognostic marker signature featuring increased abundance of LGALS3BP and decreased abundance of arachidonic acid and 5-HETE correlated with progression-free survival in these patients. This study indicates that BOLD-100 affects fatty acid/oxylipin profiles and influences systemic lipid crosstalk, which, in combination with FOLFOX chemotherapy, may at least partially account for the superior clinical outcomes over established therapies in mCRC patients.