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Median sternotomy remains a standard approach for cardiac surgery but is associated with significant postoperative pain and increased opioid requirements. Inadequate pain control may contribute to respiratory complications, prolonged mechanical ventilation, and delayed recovery. Ultrasound-guided fascial plane blocks, including the pecto-intercostal fascial block (PIFB) and the transversus thoracic plane block (TTPB), have emerged as effective components of multimodal analgesia strategies. This narrative review compares PIFB and TTPB for post-sternotomy analgesia, focusing on clinical outcomes, pharmacological properties, and interindividual variability. Available clinical studies suggest that both techniques provide comparable analgesic efficacy and opioid-sparing effects, although some evidence indicates that PIFB may be associated with reduced opioid consumption or prolonged time to first analgesic request. Anatomical differences between techniques may influence dermatomal coverage, technical complexity, and risk profile. In addition, pharmacokinetic, pharmacodynamic, and genetic factors may contribute to variability in analgesic response and should be considered when tailoring perioperative pain management strategies. Practical considerations, including operator expertise, procedural feasibility, and patient-specific factors, further influence block selection. Overall, both PIFB and TTPB are effective for post-sternotomy analgesia. Their optimal use should be guided by an individualized approach that integrates clinical evidence, anatomical considerations, and patient-specific characteristics.