This paper investigates the combined impact of depot location, fleet composition and routing decisions on vehicle emissions in city logistics. We consider a city in which goods need to be delivered from a depot to customers located in nested zones characterized by different speed limits. The objective is to minimize the total depot, vehicle and routing cost, where the latter can be defined with respect to the cost of fuel consumption and CO2 emissions. A new powerful adaptive large neighborhood search metaheuristic is developed and successfully applied to a large pool of new benchmark instances. Extensive analyses are performed to empirically assess the effect of various problem parameters, such as depot cost and location, customer distribution and heterogeneous vehicles on key performance indicators, including fuel consumption, emissions and operational costs. Several managerial insights are presented.