There is still much to learn about the predictors of therapeutic response in psychiatry, but progress is gradually being made and precision psychiatry is an exciting and emerging subspeciality in this field. This is critically important in the treatment of refractory psychotic disorders, where clozapine is the only evidence-based treatment but only about half the patients experience an adequate response. In this case report, we explore the possible biological mechanisms underlying treatment failure and discuss possible ways of improving clinical outcomes. Further work is required to fully understand why some patients fail to respond to the most effective treatment in refractory schizophrenia. Therapeutic drug monitoring together with early pharmacogenetic testing may offer a path for some patients with refractory psychotic symptoms unresponsive to clozapine treatment.