Urban overheating, driven by global climate change and urban development, is a major contemporary challenge that substantially impacts urban livability and sustainability. Overheating represents a multifaceted threat to the well-being, performance, and health of individuals as well as the energy efficiency and economy of cities, and it is influenced by complex interactions between building, city, and global scale climates. In recent decades, extensive discipline-specific research has characterized urban heat and assessed its implications on human life, including ongoing efforts to bridge neighboring disciplines. The research horizon now encompasses complex problems involving a wide range of disciplines, and therefore comprehensive and integrated assessments are needed that address such interdisciplinarity. Here, our objective is to go beyond a review of existing literature and instead provide a broad overview and integrated assessments of urban overheating, defining holistic pathways for addressing the impacts on human life. We (a) detail the characterization of heat hazards and exposure across different scales and in various disciplines, (b) identify individual sensitivities to urban overheating that increase vulnerability and cause adverse impacts in different populations, (c) elaborate on adaptive capacities that individuals and cities can adopt, (d) document the impacts of urban overheating on health and energy, and (e) discuss frontiers of theoretical and applied urban climatology, built environment design, and governance toward reduction of heat exposure and vulnerability at various scales. The most critical challenges in future research and application are identified, targeting both the gaps and the need for greater integration in overheating assessments.