The main goal of this dissertation is to propose a new analytical framework and supporting optimization models that will encourage the aviation industry to incorporate alternative transportation modes when major airports in the system encounter temporary closures or severe capacity deficiencies. This framework can provide a way to reduce passenger disutility due to delay and misconnection, to help airlines reduce operating cost and recover schedule more promptly, and to assist air traffic flow managers to utilize and distribute scarce resources more efficiently and equitably. Airline delays cost billions of dollars each year in the U.S. Most of the delays occur on days when airlinesâ€™ planned schedules are disrupted and off-schedule operations (OSO) have to be performed. One main reason for the disruptions is airspace capacity shortfall caused by adverse weather or other temporary events. It is suggested in this study that when there is a significant capacity shortfall, airlines with hub-and-spoke networks could incorporate ground transport modes into their operations. Real-time inter-modalism includes the substitution of flights by surface vehicle trips and, when the hub is part of a regional airport system, the use of inter-airport ground transport to enable diversion of flights to alternate hubs. Real-time inter-modalism is different from the air-rail cooperation currently practiced in Europe because it is only triggered by severe demand and supply imbalance at major hub airports and emphasizes operational integration of existing airside and ground transport capabilities rather than major capital investment. In the first strategy, Real-time Inter-Modal Substitution (RTIMS), airlines substitute short-haul flights with ground transport modes during severe disruptions. In this way, scarce arrival and departure slots can be used by long-haul, large jets with more passengers or other high-priority flights. As a first step, a deterministic queuing analysis is used to identify flights whose substitution by ground transport would result in net time savings, based on a comparison of the reduced flight delay and increased line-haul time that would result. Then for arrivals and departures of one airline, a mathematical programming model is constructed to help the airline make decisions on whether to cancel flights, substitute them with motor coaches, or assign them delays commensurate with airport capacity constraints. An approximation algorithm is proposed to reduce the substantial computation time required to solve large-scale non-linear integer programming problems. A set of experiments are designed to assess potential savings from ground transport substitution. Sensitivity analyses are conducted to investigate the effects of severities of capacity shortfalls, passenger value of time, distances of short-haul spoke airports, load factor of the flights, schedule peaking, and connecting patterns of transfer passengers on the optimization results and the savings from inter-modal substitution. Many major metropolitan areas are served by one or two major hub airports and several surrounding regional airports, which collectively form a regional airport system. Some of the regional airports are underutilized and contain runways long enough to serve most of the commercial aircraft types. Hence, the second strategy of inter-modalism is to divert hub-bound flights affected by capacity shortfall at the hub airport to regional airports (called alternative hubs). The strategy is termed real-time inter-modal diversion (RTIMD). In contrast to diversions currently implemented in airline operation, this strategy moves passengers between the airports as necessary to access diverted flights or make interairport connections. Toward this end, dedicated ground transportation services will be available to transport passengers between a primary hub and alternative hub. Like RTIMS, RTIMD also allows short-haul flights to be substituted by motor coaches. To implement this strategy, the alternative hub is selected based on evaluation of maximum runway length, driving distance, and correlation of weather impact and demand profiles. An extension of the mathematical programming model of RTIMS is proposed and similar approximation algorithm is used to obtain optimum results for a case study. Considering the possibility of the alternative hub being overwhelmed by diverted flights, it is suggested to enhance the current Ground Delay Program (GDP) to determine the Controlled Time of Arrivals (CTAs) at both the major hub airport and the alternative hub airports. That proposed enhanced GDP is termed Regional GDP. There are fundamental issues that need to be considered while implementing the strategies, such as motor coach service provision, passenger, security, and airport facility issues. This study identifies and assesses these issues, suggests solutions based on preliminary investigation, and highlights needs for further research and policy decision making. The inter-modal framework proposed in this thesis will substantially reduce the costs of recovering from major hub capacity shortfalls by providing alternatives to simple cancellation in airlinesâ€™ schedule perturbation recovery, thus reducing the number of disrupted passengers and the delay propagated to later flights and other parts of the network.