Metastasis is the final stage of cancer progression and responsible for more than 90% of cancer-related deaths. Effective therapeutic strategies are still lacking and resistance to current therapies pose a formidable challenge. Informed by clinical data and using functional in vivo and in vitro models, our group seeks to understand the mechanistic determinants for metastatic competence and resistance to therapies. Both rely on programs that ensure the cancer cells’ survival during periods of enhanced cellular stress, limited survival cues and attacks by the immune system. Our goal is to enhance the efficacy of current therapies using combinatorial treatment regimens and find new therapeutic avenues to fight metastatic cancer.