Aim: To summarize the current evidence on risk factors, microbiological profiles, and treatment complications associated with PJIs. By synthesizing findings from recent studies, this review identifies key challenges and areas for improvement in the prevention, diagnosis, and management of PJIs. Materials and Methods: A comprehensive literature search was conducted across major academic databases, including PubMed, Embase, and Web of Science, to identify relevant articles published between 2015 and 2025. Studies were selected based on their focus on microbial, biomechanical, and patient-related factors influencing PJI outcomes. Results: The review highlights the predominance of Gram-positive bacteria, such as Staphylococcus aureus and Staphylococcus epidermidis, as major pathogens in PJIs, with an increasing role of Candida species in complex cases. Key patient-related risk factors include obesity, diabetes, advanced age, and immunosuppression. Two-stage revision arthroplasty remains the gold standard for managing chronic PJIs, though single-stage revisions are gaining attention for specific scenarios. Emerging diagnostic biomarkers, such as calprotectin, offer potential for earlier and more accurate diagnosis, while advancements in biofilm-targeted therapies represent promising directions for treatment. Conclusions: PJIs represent a multifaceted clinical challenge requiring a multidisciplinary approach. Current knowledge underscores the importance of individualized patient optimization, standardized diagnostic protocols, and targeted antimicrobial strategies. Future research should focus on addressing knowledge gaps in diagnostic biomarkers, biofilm management, and the optimization of surgical approaches to improve patient outcomes and reduce the burden of PJIs.