The investigation of novel EGFR and BRAFV600Edual inhibitors is intended to serve as targeted cancer treatment. Two sets of purine/pteridine-based derivatives were designed and synthesized as EGFR/BRAFV600Edual inhibitors. The majority of the compounds exhibited promising antiproliferative activity on the cancer cell lines tested. Compounds5a,5e, and7eof purine-based and pteridine-based scaffolds were identified as the most potent hits in anti-proliferative screening, with GI50values of 38 nM, 46 nM, and 44 nM, respectively. Compounds5a,5e, and7edemonstrated promising EGFR inhibitory activity, with IC50values of 87 nM, 98 nM, and 92 nM, respectively, when compared to erlotinib’s IC50value of 80 nM. According to the results of the BRAFV600Einhibitory assay, BRAFV600Emay not be a viable target for this class of organic compounds. Finally, molecular docking studies were carried out at the EGFR and BRAFV600Eactive sites to suggest possible binding modes.