The layer-by-layer polyelectrolyte adsorption technique has been combined with the particle lithography technique to produce anisotropic polymer microcapsules each with a single nanoscale patch. The patch region covers roughly 5% of the capsule surface area, while the remaining 95% of the capsule surface is reinforced with a fluorescent nanoparticle shell. The nanoparticle shell maintains the capsule integrity and stability in suspension, while also providing a foundation for further ionic or covalent modification. The microcapsules are pH sensitive to loading and release, which we show by loading Rd6G red fluorescent dye, and they shrink and swell in response to solution pH. Confocal laser scanning microscopy confirms that these dual-functionalized capsules have a single precisely-placed nanoscale red region (revealing the underlying fluorescence) on an otherwise green surface (due to the nanoparticle coating). Even after the capsules are dehydrated, they re-hydrate intact and assume their original spherical morphology, demonstrating a resilient “Lazarus behavior”. The fabrication technique avoids organic solvents, is adaptable, and produces anisotropic microcapsules that are robust to many solution conditions.