Biological cells cultured in a 3D microenvironment are more realistic and exhibit characteristics found in vivo when compared to 2D cell cultures. However, culturing 3D cellular structures such as epithelial mammary spheroids and endothelial cells simultaneously is tedious using conventional cell cultureware. To address this issue, we have developed a CNC-milled microfluidic system that enables simultaneous culturing of 3D tumor spheroids and endothelial-lined lumens. We employed an accessible polishing techniques to make optical quality concave features in milled microfluidic platforms. This system can be used to potentially study the complex and dynamic cellular interactions of cancer development, angiogenesis and other malignancies involving the interactions between different cell types of different morphologies.