Structurally complex plasmonic nanoarchitectures represent an emerging class of nanomaterials with properties that extend beyond those of conventional spherical nanoparticles. Their distinctive structural motifs generate dense near field electromagnetic hot spots, expand interfacial surface area, and create biophysical environments at the nano-bio interface that can actively engage cellular signaling networks relevant to neural regeneration and aging. Despite growing interest in these platforms, a systematic, omics-guided synthesis that links nanoparticle structural features to transcriptomic programs and regenerative outcomes has been lacking. In this review, we summarize recent advances in high complexity plasmonic nanoparticle engineering and integrate published omics-based evidence of their cellular effects, organizing the discussion. Across these studies, transcriptomic analyses of nanoparticle treated neural systems consistently highlight three convergent biological themes: mitigation of oxidative stress and activation of antioxidant pathways, suppression of neuroinflammatory signaling, and induction of neuronal developmental and plasticity programs. Collectively, the omics-guided findings synthesized here suggest that structural complexity in plasmonic nanoarchitectures is not merely a synthetic achievement but a tunable determinant of cellular state, with important implications for the rational design of regenerative nanomedicines targeting neurodegenerative diseases and age-related neuronal decline.