Problem Identification: Patients with malignant wounds report pain, distress from odor and exudate, decreased self-esteem, and poor quality of life. This systematic review explores topical opioids, antimicrobials, and odor-reducing agents for preventing or managing malignant wound pain, infection, and odor. Literature Search: MEDLINE®, EMBASE, the Cochrane Library, CINAHL®, and reference lists were searched to identify relevant studies. Data Evaluation: Eligible study designs included interventions with pre-and postintervention data. Data extraction and risk-of-bias assessments were conducted using the Cochrane approach. Synthesis: No studies evaluated opioid use. Five studies (four randomized, controlled trials) evaluated topical antimicrobials for infection and odor. All studies reported clinically (but generally not statistically) significant improvements in outcomes. Conclusions: Although not as prevalent as before, 5%-10% of tumors, particularly in breast cancer, sarcoma, and melanoma, are expected to fungate. Gaps in the literature exist for use of topical opioids and antimicrobials for managing pain, odor, and infection control in malignant wounds. Implications for Research: Current recommendations for topical control of malignant wounds are based on case reports and observational studies in patients with breast cancer. Robust, controlled trials of topical opioid and antimicrobial use are warranted in patients with melanoma, breast, or head and neck cancer.