The present review aims to assess the overall marine environmental status of the Pagassitikos, a semi-enclosed gulf off the eastern Greek mainland which is very important in terms of ecological significance and national economy. According to older and more recent physical, chemical, and biological data, the gulf can be separated into three distinct areas: the northern one, which is strongly influenced by the anthropogenic activities of the city of Volos, the central which is characterized as an organic matter deposition area, and the external, which is mainly affected by the open Aegean Sea. The gulf faced severe eutrophication problems in the past, before the construction of the Wastewater Treatment Plant in the area. The monitoring project for the implementation of the Water Framework Directive (WFD) classifies the gulf as being in a GOOD trophic status, except for the eastern part which is classified as a MODERATE status. Harmful Algal Blooms are frequent in the gulf. Heavy metals do not contaminate the sediments of the northern sector of the gulf, except for Pb whose influence is moderate. Polycyclic aromatic hydrocarbons were mainly present close to the industrial zone in the northern part of the gulf. The biomarker studies show low-to-medium levels of stress. There is an overall improvement in the Ecological Quality Status of the gulf, compared to the past. Considering the scientific effort invested in the system, the Pagassitikos Gulf can be considered an ideal test case for the development of a Digital Twin using real-time and historical data to represent the past and present and numerical models to simulate future scenarios.