Optical biosensing based on the activation of fluorescent reporters offers a powerful methodology for the real-time molecular interrogation of pathology. Here we report a first-in-class, bimodal fluorescent reporter strategy for the simultaneous and highly specific detection of two independent proteases (thrombin and matrix metalloproteases (MMPs)) pivotal in the fibroproliferative process surrounding lung cancer, based on a dual, multiplexing, peptide FRET system. This sophisticated synthetic smartprobe, with a molecular weight of 6 kDa, contains two independent fluorophores and quenchers that generate photonic signatures at two specific wavelengths upon activation by target enzymes within human lung cancer tissue.