D₂ antagonism toward multimodal receptor targeting, glutamatergic modulation, and neuroinflammatory regulation. Despite the success of atypical antipsychotics, limitations such as metabolic side effects, cognitive deficits, and treatment resistance persist. Novel compounds—including third-generation antipsychotics, trace amine-associated receptor 1 (TAAR1) agonists, serotonin–dopamine activity modulators (SDAMs), and glutamatergic agents—are redefining psychopharmacology through receptor-biased signaling, synaptic plasticity enhancement, and neuroimmune modulation. This review consolidates current insights into the neuropharmacological mechanisms of emerging antipsychotics, compares their efficacy and safety profiles, and explores future directions in precision psychiatry, AI-based drug design, and neurocircuit-level therapeutics.