Reactivation of tumor-suppressing activity of p53 protein by targeting its negative regulator MDM2/MDMX has been pursued as a potential anticancer strategy. A promising dual inhibitor of MDM2/MDMX that has been developed and is currently in clinical trials is the stapled peptide ATSP-7041. The activity of this molecule is reported to be modulated in the presence of serum. Albumin is the most abundant protein in serum and is known to bind reversibly to several molecules. To study this interaction, we develop a protocol combining molecular modeling, docking, and simulations. Exhaustive docking of the peptide with representative simulated structures of human serum albumin led to the identification of probable binding sites on the surface of the protein, including both known canonical and novel binding sites. Sequence differences at putative peptide-binding sites in human and mouse albumin result in differing interaction energies with the peptide and enable us to rationalize the observed differences in vivo. In general, the findings should help in guiding the design of features in such peptides that may affect their distribution and cell permeability, opening a new window in structure-guided design strategies.