Urban heat islands pose intensifying threats to public health, equity, and urban livability as climate change amplifies temperature extremes. This systematic review synthesizes evidence from 33 primary studies (2021–2025) examining health impacts, mitigation strategies, and policy integration. The analysis focuses on interaction mechanisms, specifically how mitigation strategies differentially reduce health burdens across vulnerable populations, to advance systems-level understanding of urban heat dynamics. Following PRISMA guidelines, the review examined these mechanisms across three interconnected domains: health burdens, physical mitigation effectiveness, and post-pandemic policy synergies. Findings reveal profound inequities in heat exposure and associated health outcomes, with disadvantaged populations experiencing 26–45% higher heat-related mortality risk and 3–4 °C greater exposure than affluent communities, even after controlling for income. Physical mitigation strategies show measurable effectiveness, providing 1–6 °C cooling from green infrastructure and 2–22 °C from cool surfaces. Optimal interventions vary by socioeconomic context, with urban trees being more effective in disadvantaged areas, while cool roofs are better suited to affluent zones. COVID-19 natural experiments demonstrated 30–50% anthropogenic heat reductions, revealing strategic opportunities for integrating heat mitigation with 15-Minute City planning and work-from-home normalization. Effective implementation requires moving beyond isolated interventions toward spatially differentiated, equity-centered strategies aligned across planning, transportation, and governance domains. The post-pandemic period presents a critical window for embedding heat mitigation into broader urban transformation agendas.