Methods, systems, and apparatus, including medium-encoded computer program products, for computer aided design of physical structures using generative design processes, where the 3D models of the physical structures are produced so as to facilitate manufacturing of the physical structures using 2.5-axis subtractive manufacturing systems and techniques, include: obtaining a design space, design criteria, and in-use case(s); iteratively modifying a generatively designed shape in the design space in accordance with the design criteria and the in-use case(s) using a density-based representation of the generatively designed shape and including adjusting the density-based representation of the generatively designed three dimensional shape in accordance with a milling direction of a 2.5-axis subtractive manufacturing process in at least two iterations of the iteratively modifying; and providing the generatively designed shape for use in manufacturing a physical structure using computer-controlled manufacturing that employs the 2.5-axis subtractive manufacturing process.