The Network Fundamental Diagram (NFD) represents dynamics of traffic flow at the network level. It is exploited to design various network-wide traffic control and pricing strategies to improve mobility and mitigate congestion. This study presents a framework to estimate NFD and incorporates it for three specific applications in large-scale urban networks. Primarily, a resource allocation problem is formulated to find the optimal location of fixed measurement points and optimal sampling of probe trajectories to estimate NFD accounting for limited resources for data collection, network traffic heterogeneity and asymmetry in OD demand in a real-world network. Using a calibrated simulation-based dynamic traffic assignment model of Chicago downtown network, a successful application of the proposed model and solution algorithm to estimate NFD is presented. The proposed model, then, is extended to take into account the stochasticity of day-to-day fluctuations of OD demand in NFD estimation.Three main applications of NFD are also shown in this research: network-wide travel time reliability estimation, network-wide emission estimation, and real-time traffic state estimation for heterogenous networks experiencing inclement weather impact. The main objective of the travel time reliability estimation application is to improve estimation of this network-wide measure of effectiveness using network partitioning. To this end, a heterogeneous large-scale network is partitioned into homogeneous regions (clusters) with well-defined NFDs using directional and non-directional partitioning approaches. To estimate the network travel time reliability, a linear relationship is estimated that relates the mean travel time with the standard deviation of travel time per unit of distance at the network level. Partitioning and travel time reliability estimation are conducted for both morning and afternoon peak periods to demonstrate the impacts of travel demand pattern variations.This study also proposes a network-level emission modeling framework via integrating NFD properties with an existing microscopic emission model. The NFDs and microscopic emission models are estimated using microscopic and mesoscopic traffic simulation tools at different scales for various traffic compositions. The major contribution is to consider heterogenous vehicle types with different emission generation rates in the network-level model. Non-linear and support vector regression models are developed using simulated trajectory data of thirteen simulated scenarios. The results show a satisfactory calibration and successful validation with acceptable deviations from underlying microscopic emission model, regardless of the simulation tool that is used to calibrate the network-level emission model.Finally, the NFD application for real-time traffic state estimation in a network experiencing inclement weather conditions is explored. To this end, the impacts of weather conditions on the NFD and travel time reliability relation are illustrated through a scenario-based analysis using traffic simulation. Then, the real-time traffic state prediction framework in the literature is adjusted to capture weather conditions as a key parameter. The extended Kalman filter algorithm is employed as an estimation engine to predict the real-time traffic state. The results highlight the importance of considering weather conditions in the traffic state prediction model.