Introduction: Infection prevention and control (IPC) measures are essential to minimizing healthcare-associated infections (HAIs), reducing antimicrobial resistance (AMR), and safeguarding the well-being of patients and healthcare workers. Given the significance of IPC in healthcare settings, especially highlighted by the COVID-19 pandemic, this systematic review evaluates the effectiveness of various IPC strategies, including hand hygiene, personal protective equipment (PPE), isolation protocols, and patient education. Methods: This systematic review and meta-analysis adhered to a rigorous methodology, including a comprehensive literature search of PubMed, Embase, and the Cochrane Library for studies published between 2014 and 2024. Studies focusing on the impact of IPC measures on HAIs, AMR, and patient and healthcare worker safety in various healthcare settings were included. Data extraction and quality assessment were performed by two independent reviewers, with disagreements resolved by a third reviewer. Statistical analysis, including heterogeneity assessment using I², was conducted using STATA V.14.0, applying fixed-effect or random-effect models as appropriate. Results: A total of 11 studies met the inclusion criteria, spanning diverse healthcare settings such as hospitals, long-term care facilities, and resource-limited environments. The findings indicate that IPC measures significantly reduce HAIs and improve compliance among healthcare workers. Hand hygiene interventions and PPE use were especially effective in controlling infection transmission, though PPE use was sometimes associated with adverse effects on healthcare workers. Isolation measures, while effective, showed psychological impacts on patients, underscoring the need for supportive interventions. Economic evaluations revealed cost savings through IPC implementation, particularly in long-term care facilities, emphasizing the feasibility of IPC measures even in resource-limited settings. Conclusion: This review demonstrates that IPC measures are effective in reducing infection transmission, though challenges such as compliance, psychological impact, and ethical considerations must be addressed. Tailored strategies that account for specific healthcare settings and include patient education, psychosocial support, and ongoing staff training are recommended to optimize IPC outcomes. Further research should address limitations related to methodological diversity and potential publication bias to enhance the understanding of IPC effectiveness across diverse healthcare environments.