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(1) Background: With the increasing incidence of cancer, the need for handling cytotoxic drugs has also grown. However, manipulating these drugs exposes healthcare professionals to significant risks, including occupational exposure to hazardous chemicals. Therefore, it is important to adopt protective measures, including personal protective equipment (PPE) and correct ergonomic practices, to ensure safe drug preparation and minimize health risks for the operators. However, while chemical exposure and PPE have been extensively addressed in the literature, the combined impact of ergonomic practices and protective measures remains insufficiently emphasized, representing a critical gap this review aims to address. Accordingly, the objective of this literature review was to analyze the ergonomic and individual protection practices during the handling of cytostatic drugs and all the implications that bad ergonomic practices and/or poor individual protection have on the operator's health; (2) Methods: In order to perform this integrative review, a structured literature search was conducted using online databases (Web of Science<sup>®</sup>, Google Scholar<sup>®</sup>, and PubMed<sup>®</sup>) from January 2005 to June 2025. (3) Results: A total of 19 articles were analyzed, with 17 focusing on PPE and 17 on ergonomics. The findings emphasize that PPE, such as gloves, masks, gowns, sleeves and safety glasses, plays a critical role in the safe handling of cytotoxic drugs, particularly when combined with other safety measures. Additionally, maintaining correct ergonomic posture is important in preventing musculoskeletal disorders; (4) Conclusions: This review emphasizes the significance of integrating appropriate PPE use with sound ergonomic procedures. Although PPE is still the secondary line of defense against occupational exposure, ergonomic issues must also be addressed to avoid chronic musculoskeletal problems. Continuous training, rigorous attention to safety procedures, and ergonomic enhancements should be prioritized by healthcare facilities as a key element of occupational safety programs to reduce the short-term and long-term health hazards for personnel handling dangerous drugs.