Background/Objectives: Sepsis and septic shock are critical conditions associated with high mortality rates and substantial impacts on healthcare systems. Accurate and rapid diagnosis is essential for the management of these conditions. The objective of this study is to assess the accuracy of contemporary and traditional methods for diagnosing sepsis and to determine whether improvements have been made concerning the integration of novel diagnostic approaches, to facilitate a prompt diagnosis, taking into account the rapid progression of complications associated with this disease. For this purpose, studies published between 2014 and 2024 were examined to highlight the benefits and limitations of each approach. Methods: A systematic literature review was conducted, including randomized clinical trials, observational studies, and retrospective studies assessing both conventional diagnostic methods (blood cultures and clinical scoring systems) and modern methods (rapid molecular tests, specific biomarkers, and machine learning algorithms). The studies included were selected based on strict design and methodology criteria to ensure a rigorous comparative evaluation of the interventions and technologies used in diagnosing and monitoring patients with sepsis. Results: A total of 23,822 patients were reviewed across the studies included in this systematic analysis. Modern methods, such as continuous monitoring through integrated biosensors and the use of molecular panels for pathogen detection, demonstrated high potential for the early and accurate diagnosis of sepsis. The reviewed studies suggest that these methods can significantly reduce diagnostic time and improve the ability to stratify mortality risk compared to conventional methods. Conclusions: Integrating modern diagnostic technologies, such as rapid pathogen identification tests and specific biomarkers, may complement traditional methods and bring significant benefits in the management of sepsis.