Tumor vasculature is highly dynamic, dense, and non‐homogeneous. These features make it difficult to identify key determinants of tumor angiogenesis and remodeling at the single vessel level. To overcome this problem, we isolated growing tumors from the host tissue, by placing a perforated PDMS disk between the tumor and the dorsal skin in transparent windows in mice. Using this model we are able to observe and quantify various processes and stages of network formation. Between days 9–14 microvascular sprouts emerged from the perforations/holes and merged to form loops in and out of holes. Later, sprouts led by tip cells separated from the perfused, looping vessels. Surprisingly, many of the sprouts migrated away from the tumor, instead connecting to sprouts from other holes or from the edge of the PDMS disk. At day 19, smooth muscle cells were associated with the larger vessel connecting two holes. Other changes were observed after treatment with a VEGF inhibitor. In the first two days, feeding vessels dilated, but within 1–2 weeks, large vessels constricted and smaller branches are pruned. This was associated with dramatic changes in flow direction, increased perfusion and flow interruption in some vessels. The experimental model offers a novel approach for identifying key steps in tumor vascularization so that more effective and specific targeting strategies can be developed. Supported by NIH R01CA149285.