(1) Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Frailty and cardiovascular diseases are intertwined, commonly sharing risk factors and exhibiting bidirectional relationships. The relationship of frailty and non-acute myocardial infarction with cardiogenic shock (non-AMI-CS) is poorly described. (2) Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for non-AMI-CS. We classified them into frail and non-frail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. (3) Results: A total of 503,780 hospitalizations for non-AMI-CS were identified. Most hospitalizations involved frail adults (80.0%). Those with frailty had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 2.03–2.20, p < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, such as acute kidney injury, delirium, and longer length of stay. Importantly, non-AMI-CS hospitalizations in the frail group had lower use of mechanical circulatory support but not rates of cardiac transplantation. (4) Conclusions: Frailty is highly prevalent among non-AMI-CS hospitalizations. Those accompanied by frailty are often associated with increased rates of morbidity and mortality compared to those without frailty.