Inborn errors of immunity are now understood to encompass manifold features including but not limited to immunodeficiency, autoimmunity, autoinflammation, atopy, bone marrow defects, and/or increased malignancy risk. As such, it is essential to maintain a high index of suspicion, as these disorders are not limited to specific demographics such as children or those with recurrent infections. Clinical presentations and standard immunophenotyping are informative for suggesting potential underlying etiologies, but integration of data from multimodal approaches including genomics is often required to achieve diagnosis.