<p>Lateral flow devices (LFDs) rely on porous materials to guide liquid transport, and electrospun fiber mats have emerged as attractive candidates due to their high surface area, tunable porosity, and ease of functionalization. However, conventional electrospun nanofibers often deform or dissolve when exposed to heat or to solvents commonly used in biochemical assays, limiting their applicability. To address this challenge, we developed electrospun poly(methyl methacrylate) (PMMA) nanofibers that are both heat-stable and solvent-resistant through the incorporation of photoreactive groups and subsequent solid-state crosslinking via the C, H-insertion crosslinking (CHic) reaction. PMMA fibers containing methacryloyloxy benzophenone (MABP) units were rapidly activated with UV light, yielding nanofiber mats that retain their morphology under elevated temperatures and also in solvents typically used in biochemical assays. Beyond mechanical and chemical stability, we demonstrate that the surface energy of these fibers can be precisely tuned through the formation of a crosslinked hydrogel sheath composed of dimethyl acrylamide (DMAA) and MABP comonomers. This sheath can be applied either by dip-coating of mats of pre-formed fibers or by coaxial electrospinning, and becomes covalently integrated with the fiber core upon light activation. The resulting core–sheath structure transforms the originally hydrophobic PMMA mat into a highly hydrophilic, paper-like material capable of supporting controlled capillary flow. These robust and tunable nanofiber mats offer new opportunities for the design of lateral flow devices with improved solvent compatibility, thermal stability, and flow performance.</p>