Presented are footwear sole structures with pressure-mapped midsole topographies and inlaid wear-mitigating outsoles, methods for making/using such sole structures, and footwear fabricated with such sole structures. An article of footwear includes an upper for receiving and attaching to a foot of a user, and a sole structure attached to the upper for supporting thereon the user's foot. The sole structure includes a midsole that is formed with a first material having a first hardness, and an outsole that is mounted to the midsole and formed with a second material that is harder than the first material. The midsole has a ground-facing surface with multiple cavities, multiple channels interspersed with the cavities, and ground-contacting land segments that separate the cavities from the channels. The outsole is disposed in the channels and positioned between the cavities such that a ground-contacting outsole surface is substantially flush with the midsole's ground-contacting land segments.