Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.