Lung adenocarcinoma (LUAC), a subtype of non-small cell lung cancer, remains a major clinical challenge in Australia, where late-stage diagnosis contributes to a dismal 3% survival rate. In our search for novel therapeutic targets, we identified that the orphan G protein-coupled receptor bombesin 3 (BB3) is selectively expressed in LUAC, yet absent in healthy adult tissue—highlighting a unique opportunity for targeted intervention. Bioinformatics confirmed BB3 expression in 83% of LUAC cases, surpassing all known LUAC markers, with no appreciable expression in healthy adults. However, BB3 mRNA did not correlate with patient survival or known oncogenic drivers. We used selective peptide and synthetic agonists and antagonists to characterise BB3 pharmacology in HEK293 cells overexpressing BB3-eYFP, and in a panel of LUAC cell lines expressing varying levels of BB3 (with or without BB1 and BB2). Functional assays revealed that BB3 agonism or antagonism did not influence LUAC cell survival or enhance the efficacy of current treatments. Instead, BB3 exhibited constitutive activity and signalled through multiple canonical GPCR pathways, suggesting the presence of an allosteric binding site. Our findings affirm BB3’s remarkable tissue selectivity and prevalence in LUAC, while also confirming its non-oncogenic role—supporting its use as a conduit for targeted cytotoxic delivery or antibody-mediated cell death. With our detailed pharmacological insights, we are now poised to develop BB3-directed therapies. Future work will focus on receptor internalisation, structural mapping of orthosteric and allosteric sites, and computational design of ligand-drug conjugates for precision oncology.