The snail Pseudosuccinea columella is one of the main vectors of the medically-important trematode Fasciola hepatica. In Cuba, the existence of natural P. columella populations that are either susceptible or resistant to F. hepatica infection offers a unique snail-parasite for study of parasite-host compatibility and immune function in gastropods. Here, we review all previous literature on this system and present new “omic” data that provide a molecular baseline of both P. columella phenotypes from naïve snails. Comparison of whole snail transcriptomes (RNAseq) and the proteomes of the albumen gland (2D-electrophoresis, MS) revealed that resistant and susceptible strains differed mainly in an enrichment of particular biological processes/functions and a greater abundance of proteins/transcripts associated with immune defense/stress response in resistant snails. These results indicate a differential allocation of molecular resources to self-maintenance and survival in resistant P. columella that may cause enhanced responsiveness to stressors (i.e. F. hepatica infection or tolerance to variations in environmental pH/total water hardness), possibly as trade-off against reproduction and the ecological cost of resistance previously suggested in resistant populations of P. columella.