-Patients must have established and confirmed diagnosis of intermediate or adverse-risk AML

-Previously untreated AML excluding hydroxyurea and all-trans retinoic acid (ATRA).

-Age ≥ 18 years.

-Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

-Patient is able to swallow oral medications

-Patient must have a body weight of at least 50 kg

-Chronic kidney disease (CKD)-epidemiology collaboration (EPI) glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m^2

-Lab draws within certain levels

-Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

-For patients with chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy.

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

-Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

-Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function.

-The effects of iadademstat on the developing human fetus are unknown. For this reason females of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation

-Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

-Patients are willing and able to receive intensive induction chemotherapy

-Patients have isolated myeloid sarcoma or acute promyelocytic leukemia (APL)

-Patients who have not recovered from adverse events of grade 3 or more due to prior anti-cancer therapy

-Patients who are receiving any other investigational agents

-Patients who have active central nervous system (CNS) involvement by AML

-Patients who have disseminated intravascular coagulopathy with active systemic bleeding or venous or atrial signs of thrombosis

-Patients who require treatment while on study with concomitant drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline) except for drugs that are considered absolutely essential for the care of the patient and with appropriate treatment monitoring

-Patients with manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of oral drugs.

-History of allergic reactions attributed to compounds of similar chemical or biologic composition to iadademstat, azacitidine, mannitol, or venetoclax

Iadademstat Concomitant Medication Considerations:

-Patients should not use strong CYP3A inhibitors with the exception of antifungals for which standard of care (SOC) dose modifications of venetoclax exist

-Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.

-As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control.Patients with uncontrolled infection shall not be enrolled until the infection is treated and brought under control

-Pregnant women are excluded from this study