The emergence of high-throughput approaches has had a profound impact on personalized medicine, evolving the identification of inheritable variation to trajectory analyses of transient states and paving the way for the unveiling of response biomarkers. The utilization of the multi-layered pharmaco-omics data, including genomics, transcriptomics, proteomics, and relevant biological information, has facilitated the identification of key molecular biomarkers that can predict the response to therapy, thereby optimizing treatment regiments and providing the framework for a tailored treatment plan. Despite the availability of multiple therapeutic options for chronic diseases, the highly heterogeneous clinical response hinders the alleviation of disease signals and exacerbates the annual burden and cost of hospitalization and drug regimens. This review aimed to examine the current state of the pharmaco-omic approaches performed in psoriasis, a common inflammatory disease of the skin. We sought to identify central studies that investigate the inter-individual variability and explore the underlying molecular mechanisms of drug response progression via biological profiling in psoriatic patients administered with the extended therapeutic armamentarium of psoriasis, incorporating conventional therapies, small molecules, as well as biological drugs that inhibit central pathogenic cytokines involved in the disease pathogenesis.