The spatiotemporal variation in taxonomic indices and functional traits of the nematode fauna was investigated along two major environmental (salinity and organic matter enrichment) gradients in the Cabras Lagoon (Sardinia, Italy). We aimed to assess, for the first time in a transitional system of western Mediterranean Sea, how taxonomic and functional components of nematode assemblage respond to such environmental factors. The taxonomic structure was the most sensitive metric to document changes in the nematode assemblage, showing significant differences in relation to all the factors and their interactions. All the taxonomic and functional nematode features, except for the maturity index (MI), proved salinity and organic enrichment to be the primary drivers of nematode distribution. The lack of significant variation in the MI is quite interesting and can be interpreted because of the marked adaptation of nematodes to highly dynamic environmental conditions of brackish and confined habitats. Temperature mainly affected faunal composition, abundance, and diversity, due to its influence on fecundity and biological cycles on almost all species. Integrating the taxonomic and functional components of nematodes as “two-sides of the same coin”, the Shannon diversity index, the percentage of coloniser–persisters and the MI were used together to assess the Ecological Quality Status (EQS) of the study sites, which ranged from poor to bad. Nematodes proved to be good indicators of the environmental variations in the investigated lagoon ecosystem. Importantly, the joint use of taxonomic and functional approaches provided integrative knowledge of nematode response to environmental gradients. We conclude that combining nematode-based taxonomic and functional indicators represent a valuable tool to assess the environmental quality of lagoonal ecosystems and may provide complementary information to macrofauna.