Pathological assessment of the tumor-immune microenvironment is a key step in the development of a therapeutic approach for metastatic melanoma, which can respond to targeted therapy or immune checkpoint blockade depending on the specific features of the tumor. However, biopsy of metastatic lesions is invasive, and the localization of metastatic lesions to difficult-to-access sites complicates the sampling process. The cover depicts multiplex immunofluorescence of a melanoma biopsy (PD-L2/FITC in green, PD-L1/Cy3 in yellow, CD4/Cy5 in red, and CD8/Cy7 in purple). In their report, Aoude and colleagues demonstrate a novel radiomics approach to reliably qualify the molecular features of melanoma metastases normally assessed by biopsy, demonstrating that PET/CT imaging markers correlate with known biomarkers of patient response to targeted therapy and immune checkpoint blockade. The authors argue that this approach presents a noninvasive and cost-effective method to establish prognoses for metastatic melanoma patients. For more information, see the article on page 950.