Signal transducer and activator of transcription 3 (STAT3) is a transcription factor critical for cellular growth, differentiation, immune function, metabolism and survival. Constitutive STAT3 activation is associated with ~50% of human cancers, and has been linked to tumour progression and therapeutic resistance. A key target of STAT3 is MYC oncogene which is highly amplified in ~40% of tumours. The STAT3-dependent induction of MYC expression in tumours is a key event in STAT3-driven tumourigenesis. Therefore, STAT3 is presumed to be redundant in MYC-amplified tumours in which MYC expression is not responsive to STAT3. To determine STAT3 requirement in MYC-driven tumours, we generated a Myc-driven mouse model of small cell lung cancer (SCLC). Here, intranasal delivery of adenoviral-Cre induces Myc overexpression from the Rosa26 locus specifically in the lungs. These mice were crossed with Stat3 conditional mice resulting in simultaneous Myc overexpression and Stat3 deletion. MYC amplification is observed in up to 30% of SCLC patients; however, this is always in combination with universal loss in RB1 and TP53 tumour suppressor genes. Therefore, we also generated more clinically relevant mouse models that contained Myc overexpression and deletion in pRb and Trp53 (RPM mice) with or without Stat3 loss. We performed immunohistochemical analysis on primary and metastatic tumours that formed in these mouse models. Our data show that Stat3 deletion corresponds to decreased primary tumour burden in both the Myc-amplified and the RPM mice. However, we observed a significant increased liver metastasis in RPM mice following Stat3 deletion. This is accompanied by an increased lipid accumulation in the liver. We cultured primary tumour cell lines derived from our mouse models and observed that Stat3 loss leads to increased expression of enzymes involved in lipogenesis. Finally, RNA sequencing and metabolomics reveal changes in immune response and pyrimidine metabolism signatures. Together, our data show that STAT3 is crucial for the primary tumour onset in MYC-driven SCLC. However, STAT3 concomitantly increases lipogenesis and liver metastasis.