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Penetrating injuries of the heart, named penetrating cardiac injury (PCI), may cause hemorrhagic shock as well as cardiac tamponade, leading to death if not treated immediately. This systematic review aims to highlight the main aspects of penetrating cardiac injuries after firearm wounds. The cases of 39 subjects (age 37.05 + 15.4) were selected (6 fatal cases). Specifically, 4/39 cases involved subjects under 18 y.o.; analyzing the entrance wound, in 30/39 cases it was located in the anterior chest, 4/39 in the posterior chest, 3/39 in the shoulder/axilla area, 1/39 in the neck, and 1/39 in the pelvis (gluteus). The exit wound was found in only 3/39 cases. Several factors may influence the prognosis: firstly, prompt intervention represents a crucial point, then considering the complications related to PCI, the most important are myocardial infarction, and projectile migration with embolization. The mortality rate is related to: (1) area and severity of the heart injury; (2) duration of transport and intervention; (3) contemporary lesion to other organ/s; (4) the quantity of blood lost; (5) and presence/absence of cardiac tamponade. Based on these findings, a correct approach in the management of PCI may be considered important from a forensic point of view, both as regards to medical liability and from the trial perspective.