Perioperative bleeding remains a major complication in cardiac surgery and is associated with increased morbidity, mortality, and transfusion requirements. While patient blood management strategies and goal-directed hemostatic therapies have improved outcomes, the role of fundamental physiological conditions such as acid-base balance, temperature, calcium homeostasis, and hematocrit remains underexplored in clinical research. These factors may critically modulate coagulation and influence the efficacy of hemostatic interventions. This comprehensive narrative review assesses the in vitro and in vivo impact of acidosis, hypothermia, hypocalcemia, and anemia on hemostasis and proposes the concept of a coagulation-friendly environment as a prerequisite for effective bleeding management in cardiac surgery. Optimization of these variables represents an essential foundation for effective hemostatic therapy and may improve bleeding outcomes when integrated into patient blood management strategies.