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 for an object to be manufactured, design criteria, and load case(s); iteratively modifying a generatively designed 3D shape of the modeled object, including generating 2D profile representations (corresponding to discrete layers) of an updated version of the 3D shape, extruding the 2D profile representations along the milling direction, and forming a next version of the 3D shape of the modeled object from a combination of the 3D representations produced by the extruding; and providing the generatively designed 3D shape of the modeled object for use in manufacturing the physical structure using a 2.5-axis subtractive manufacturing process.