The term “gateway” refers to a city, or to some transport and logistics-oriented area in a city, that is associated with goods movement in, out, and through the area. Although the definition of a gateway is typically focused on goods movement, a more holistic view is adopted with consideration of the movements of people and the environmental implications of all movements. The relevance of this view is based on the interdependence of commercial and persons mobility, because all moves are happening within the same transport network, and is based on considerations of quality of life in a gateway city. Hamilton, Ontario, Canada, was chosen to test these concepts. Hamilton had a suitable geographical location, a busy port, an international airport, good highway and railway access, and an educated labor force. The gateway prospects for Hamilton were given perspective through a study of other prominent gateways that distilled success factors. Analytical work focused on multiregional economic impact modeling to assess the direct and indirect effects of Hamilton's potential evolution as a gateway. Local-level analysis, through integrated urban modeling and simulation of scenarios, stressed the impact of gateway development on commercial goods movement, auto commuting levels, emission levels, and transit ridership. Increased emissions resulting from gateway economic development could be overcome with forward-thinking policy focused on the uncongested movement of goods and people, compact urban form, and enhanced public transit working in concert. The addition of light rail transit in Hamilton and the promotion of a compact urban form would be catalysts for sustainable local gateway development. Finally, gateway-oriented development in Hamilton will cause noticeable regional economic growth. The models that were developed can be calibrated for other cities, given appropriate data.