Early-onset schizophrenia (EOS) is a heterogeneous condition that has a serious, insidious clinical course and poor long-term mental health outcomes. The clinical presentations are highly complex due to the overlapping symptomatology with other illnesses, which contributes to a delay in the diagnosis. The objective of the review is to study if an earlier age of onset (AAO) of EOS has poor clinical outcomes, the diagnostic challenges of EOS, and effective treatment strategies. The review provides a comprehensive literature search of 5966 articles and summarizes 126 selected for empirical evidence to methodically consider challenges in diagnosing and treating EOS for practicing clinicians. The risk factors of EOS are unique but have been shared with many other neuropsychiatric illnesses. Most of the risk factors, including genetics and obstetric complications, are nonmodifiable. The role of early diagnosis in reducing the duration of untreated psychosis (DUP) remains critical to reducing overall morbidity. Many specific issues contribute to the risk and clinical outcomes. Therefore, issues around diagnostic ambiguity, treatment resistance, nonadherence, and rehospitalizations further extend the DUP. There is hesitancy to initiate clozapine early, even though the empirical evidence strongly supports its use. There is a growing body of research that suggests the use of long-acting injectables to address nonadherence, and these measures are largely underutilized in acute settings. The clinical presentations of EOS are complex. In addition to the presence of specific risk factors, patients with an early onset of illness are also at a higher risk for treatment resistance. While there is a need to develop tools for early diagnosis, established evidence-based measures to address nonadherence, psychoeducation, and resistance must be incorporated into the treatment planning.