Tumor microcirculation exhibits structural and functional heterogeneity which influences tumor development and treatment efficiency. Here, the importance of changed vascular adaptation characteristics for tumor microvascular properties was investigated. Healthy and tumor vascular networks were visualized by intravital microscopy. A model simulation was used to estimate pressure (P), flow (Q), and shear stress ([tau]) for all vessel segments. Diameter adaptation in response to hemodynamic (P,Q), metabolic (pO2), and conducted stimuli was predicted. Adaptation characteristics optimized for healthy mesentery microvascular beds ("standard adaptation") and "tumor adaptation rules" (reduced hemodynamic sensitivity, information transfer and randomized metabolic sensitivity) were used. Oxygen deficit (OD, % O2 supply/demand mismatch) and area difference between draining and feeding vessels at branch points ([Delta]A) were calculated. Without simulated adaptation, OD and [Delta]A in mesentery networks were low relative to tumor networks (0.12/0.85 vs. 0.24/4.46). Upon simulated standard adaptation, OD and [Delta]A values for normal and tumor networks converged: 0.012/0.56 vs. 0.167/0.37; also, tumor adaptation led to high OD and [Delta]A for normal networks (0.262/1.34). Thus typical functional properties of tumor microvascular networks may result from specific changes in vascular adaptation evoked by hemodynamic and metabolic stimuli.