Cardiogenic shock (CS) is a life-threatening condition characterized by severe systemic hypoperfusion that may progress into multi-organ failure. Immediate optimization of organ perfusion is therefore considered a critical priority. However, first-line therapy with inotropes and vasopressors carries significant risks, adding stress to an already severely failing heart, and may eventually contribute to further clinical deterioration. Subsequent temporary mechanical circulatory support (tMCS) has been traditionally viewed upon as a means to restore systemic circulation. Recent approaches have, however, suggested that the hemodynamic buffer provided by tMCS may create a therapeutic window for the initiation of evidence-based heart failure therapies. Nevertheless, interfering in a jeopardized hemodynamic and failing homeostasis is extremely challenging and the devices carry a significant risk of serious adverse events. In this review, we discuss the potential use of heart failure therapies in patients with CS who are supported with tMCS. We highlight the feasibility and potential efficacy of this combined therapeutic approach from the perspective of a novel, aviation-inspired safety framework referred to as the ‘hemodynamic envelope’. This concept may inspire future study designs and support clinicians in initiating established heart failure therapies during tMCS.