<p>Background: Bone flap replacement restores cranial protection and contour in neurosurgery. Accidental intraoperative contamination, particularly dropped bone flaps, poses risks of infection. Management strategies are heterogeneous and lack standardized guidelines. Objective: To systematically review reported strategies for managing dropped cranial bone flaps, focusing on surgical context, decontamination methods, operative impact, antibiotic use, and outcomes. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Relevant databases were searched from inception to September 2025. Eligible studies described strategies for intraoperative bone flap decontamination and reported at least one clinical outcome. Data extracted included study type, sample size, surgical context, decontamination strategy and duration, post-operative antibiotic regimen, follow-up period, and outcomes. Results: Three retrospective series comprising 48 cases met the inclusion criteria. Flaps were dropped during elevation, transfer, drilling, reinsertion, and plating. Chemical decontamination—typically saline irrigation, povidone iodine ± hydrogen peroxide, and antibiotic soak—was most common, adding 15–30 min to surgery, with no post-operative infections reported. Autoclaving ensured sterility but prolonged the operative time (37 min), and carried the risk of partial flap resorption. Discarding the flap with immediate cranioplasty was reserved for non-salvageable cases, incurring the longest delay (39 min). Conclusion: Dropped cranial bone flaps are rare but have clinically significant implications. Available evidence, limited to small series and surveys, show comparable outcomes between chemical decontamination, autoclaving, and discarding the flap followed by cranioplasty. Standardized, evidence-based guidelines are lacking, underscoring the need for multicenter prospective studies.</p>