Virus infection and oncogenesis are two tightly linked processes. Some viruses are endowed with a direct transforming capability and infection activates inflammation that, in turn, favours tumor progression. Also, both inflammation and tumor trigger (and are strongly dependent from) angiogenesis. Finally, some oncogenic viruses release "virokines" that contribute to the development of virus-associated tumors. At a molecular level, viral proteins, cytokines, receptors and adhesion molecules "cross-contribute" to the different processes and, amazingly, many of them bind to heparin and to heparan sulfate proteoglycans to exert their functions. Heparin-like polysulfated (PS) or polysulfonated (PSN) compounds are an heterogeneous group of natural or synthetic molecules whose prototypes are PS heparin and PSN suramin. They vary in their backbone structure, length, number/disposition of sulfated/sulfonated groups. Different combinations of these features confer to PS/PSN the capacity to bind with variable specificity to those heparin-binding proteins that "cross-contribute" to virus infection and tumor progression. Taken together, these considerations suggest that heparin-like PS/PSN antagonists may act as multitarget drugs that may control at once virus infection and tumor progression by targeting different proteins simultaneously. Here we discuss the possibility to exploit PS/PSN compounds for the development of drugs at the cross-road of viral infection and oncogenesis, taking in consideration the past efforts, possible drawbacks and future perspectives.