The World Health Organization has identified oncological diseases as one of the most serious health concerns of the current century. Current research on oncogenesis is focused on the molecular mechanisms of energy-biochemical reprogramming in cancer cell metabolism, including processes contributing to the Warburg effect and the pro-oncogenic and anti-oncogenic roles of sirtuins (SIRTs) and poly-(ADP-ribose) polymerases (PARPs). However, a clear understanding of the interaction between NAD+, SIRTs in cancer development, as well as their effects on carcinogenesis, has not been established, and literature data vary greatly. This work aims to provide a summary and structure of the available information on NAD+, SIRTs interactions in both stimulating and countering carcinogenesis, and to discuss potential approaches for pharmacological modulation of these interactions to achieve an anticancer effect.