The medical community generally identified a rising amount of patients with primary immune deficiency (PID) and cardiovascular system (CVS) comorbidities last year. These CVS malformations might be explained by infectious or autoimmune etiologies, genetic aspects, and the immune system participating in the CVS tissue development. Here, we describe combinations of immune and CVS defects from comprehensive literature. In addition to some famous combinations of PID with CVS abnormalities, such as DiGeorge syndrome and CHARGE anomaly, here are described CHD in combination with Omenn syndrome, DNA repair defects, common variable immunodeficiency, Roifman syndrome, and others. Moreover, we describe the vascular anomalies in chronic mucocutaneous candidiasis, chronic granulomatous disease, and Wiskott–Aldrich syndrome. In conclusion, the expanding range of PID needs advanced attention to the potential CVS involvement as an essential benefactor in diagnosing and managing the disease.