With careers increasingly taking place within and between cities, this article maps the territory for research and theory on careers in cities. Cities present a microcosm for advancing a systemic understanding of people’s careers over time and in relation to broader issues. We acknowledge cities’ multilayered contexts by identifying six spheres—locality and networks, material infrastructure, economic activities, non-work, virtual reconfiguration, and nexus of social change. The interplay between careers and these city spheres informs intertwined phenomena such as well-being, mobility, and migration. To guide further research, our framework distinguishes two meta-theoretical perspectives. An entity perspective examines causal relationships across levels, analyzing how urban characteristics explain career-related phenomena, and vice versa. A constructionist perspective examines how people’s construal of careers in cities draws on cultural repertoires about work, non-work life, and the city, including its social, symbolic, and material aspects. We use the framework to discuss contributions of the five articles of this special issue. A career lens can contribute to our understanding of cities being sources of both stability and change. With cities currently facing significant disruptions, there has never been a more appropriate time for careers researchers to incorporate the city as context.