A popular point-of-care diagnostic method is lateral flow immunoassay (LFIA) with gold nanoparticles (AuNPs) as a signal tracer. However, considering the weak absorbance of conventional AuNPs, the poor sensitivity has greatly limited the wide application of AuNPs-LFIA. With the development of nanomaterials, the engineering of multifunctional composite nanomaterials (NPs) with synergistic size tuning and shape engineering provides extraordinary opportunities to improve the sensitivity of LFIA. Taking advantage of the electronic effects of three kinds of metallic elements including Ag, Pd, and Cu, trimetallic-alloys AgPdCu hollow nanospheres (AgPdCuHNs) with crystal defects was prepared, featuring excellent colorimetric signal (α = 6.6 L/g cm−1), outstanding photothermal properties (η = 75.64 %), high antibody coupling efficiency (96.31 %), and unrestricted immunorecognition affinity (Ka = 2.366 × 109 M−1), all of which are conducive to a highly sensitive dual-signal transduction mode. A colorimetric-photothermal dual-response immunoassay was constructed with AgPdCuHNs achieving colorimetric and photothermal detection limits of 0.071 and 0.018 ng mL−1 for Albendazole monitoring, which were approximately 4- and 15-fold lower than that of AuNPs-LFIA (0.279 ng mL−1), respectively. This study demonstrates the effectiveness of AgPdCuHNs-LFIA in establishing high-performance sensing and can be extended to a wide range of future point-of-care testing applications.