Earlier conducted systematic reviews have focused on the important impact of synthetic lethality (SL) application in managing various types of tumors, classifying SL, methods for assessment, and technological advances in SL inhibitions and examining the preclinical and clinical landscape of SL cancer biology, and neither of those investigations presented the molecular pathway description of the recommended lethal target of SL in cancer. Out of 36 gene expression omnibus (GEO) database sets selected from 343 retrieved (2023 to 2024), 11 were excluded, and 25 were included in the study and presented in the review. Beyond the search, few interesting database sets comprising interesting molecular pathway were included in minority. Molecular pathways pictures of the proposed SL targets for the cancer condition were prepared for lucid understanding of the oncology disease fundamental mechanism behind the SL concept. SL approach benefits have been demonstrated in cancer. Thus, the current exploration suggests that SL approach of molecular investigations should be expanded to include other specialists including cardiovascular and nephrology to fully explore the benefits of society.