The concomitant use of HAART and AC may be associated with an incresead risk of toxicity secondary to pharmacokinetic and pharmacodynamic interactions mediated by drug-metabolizing enzymes or transporters leading to altered drug exposure. For the majority of antiretroviral drugs that are cytochrome P (CYP) 450 substrates, inducers or inhibitors, co-administration with other metabolized drugs could result in drug accumulation and possible toxicity or decreased efficacy of one or both drugs. Same studies have shown that intensive antiblastic chemotherapy (AC) treatment are feasible in HIV-infected patients with cancer and the outcomes is similar to that of HIV-negative patients receiving the same AC regimens. For these reasons it is important that HIV patients affected by cancer underwent to HAART/AC should be individualized according to the regimen treatment selected, liver or renal function, bone marrow suppression, and others co morbidities. The purpose of this review is to summarize existing data on the impact of individual pharmacogenetic profile in order to optimize the clinical management of cancer patients with HIV/AIDS and between antiretrovirals and AC. Based on the individual genetic profiles, the oncologist will have a new features with which to make personalized treatment decision for their patients in order to maximize benefit and minimize toxicity.