The imperative of patient safety in healthcare takes a central stage, more so in the context of Nigeria. This review aims to provide a comprehensive understanding of the patient safety landscape in Nigeria, drawing on 12 empirical studies. This study aims to elucidate the multifarious challenges and barriers health-care professionals encounter in Nigeria concerning patient safety. Concurrently, it delves into the prevailing patient safety culture and the factors shaping it. This study used secondary data to conduct a systematic review of existing literature; 12 studies, spanning from 2015 to 2022, were meticulously examined. These explorations cover a broad spectrum of patient safety aspects in Nigeria, focusing particularly on the insights of nurses and doctors. Through the use of thematic analysis, the studies’ synthesis illuminates a significant gap between the envisioned safety protocols and their on-ground realization. Exacerbating this challenge is the acute lack of resources, which invariably hampers the quality of care. In addition, barriers to effective communication and inadequate reporting mechanisms emerge as significant obstacles. The deficiencies in consistent training and education are also prominent, which stand as potential vulnerabilities in the system. The palpable need for heightened awareness, emphasis on recurrent training initiatives, and strict adherence to established safety guidelines are amplifying these concerns. It was, thus, concluded that the healthcare trajectory in Nigeria, as informed by this review, underscores a pressing need for systemic interventions to elevate patient safety standards. Such a transformative journey demands the concerted efforts of all stakeholders, fostering an environment that prioritizes patient safety and enhances the overall trust in Nigeria’s healthcare system.