Here we report in detail the management of three complex advanced BCC (aBCC) cases treated with nivolumab and pembrolizumab after vismodegib failure. All patients were treated with PD-1 inhibitors before cemiplimab was approved by the FDA and EMA. On all tumors next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed and subsequently patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anti-cancer drugs based on the molecular tumor profile.