As the current pandemic has shown, lateral flow assays (LFAs) are a prime example of point-of-care devices enabling quick testing at an affordable price. However, their ease of use undeniably affects their sensitivity, making them less sensitive than other multi-step and time-consuming diagnostic assays, such as polymerase chain reactions and enzyme-linked immunosorbent assays. A possible solution to overcome this lack of sensitivity is the exploitation of bottom-up approaches to synthesize nanomaterials with outstanding properties for use as colorimetric labels in LFAs, that is, using nanoparticles with better optical capabilities to improve the generation of the colorimetric signal and the overall sensitivity of LFAs. Following this strategy, we rationally optimized the synthesis of gold and iridium oxide nanoflowers (Au–IrO2 NFs) to enhance their physical–chemical properties as colorimetric labels in LFAs. Specifically, we were able to rationally control their size (from 155 to 53 nm in diameter) in order to guarantee an optimal flow along the different pads of a LFA. Moreover, thanks to their superior plasmonic behavior (compared to standard AuNPs), we could achieve an 8.5-fold lower limit of detection (down to 1.2 ng/mL) for human immunoglobulin G (HIgG) than standard LFAs (10.1 ng/mL). Therefore, due to their optical and redox properties, bioconjugation capabilities, and synergic combination of the individual components, Au–IrO2 NFs appear as potential candidates for the next generation of optical LFAs.