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While clear-cut cases of acute myocardial infarction typically require immediate invasive coronary angiography (ICA), more nuanced and complex presentations require careful selection of the most appropriate diagnostic tests to determine the underlying cause of symptoms. This narrative review aims to delineate specific scenarios in which non-invasive multimodal imaging techniques\u2014such as transthoracic echocardiography (TTE), coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and nuclear imaging\u2014are appropriate and optimal in the setting of ACS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent findings<\/jats:title>\n                    <jats:p>In the initial assessment of a patient with suspected ACS, TTE is essential to identify regional wall motion abnormalities (RWMA) with a typical \u201ccoronary pattern\u201d. In recent years, the use of speckle tracking echocardiography has been shown to increase diagnostic sensitivity in this setting, particularly in patients without overt RWMA. Stress echocardiography also holds diagnostic value in specific low-risk ACS settings. Moreover, in this patient population, CCTA has demonstrated a very high negative predictive value (NPV) across multiple trials, effectively reducing the number of unnecessary ICA. Recently, this technique has been enhanced by the ability to perform qualitative analysis of atherosclerotic plaque, allowing the identification of high-risk features associated with instability and rupture, and thus with ACS. Finally, CMR enables myocardial tissue characterization, which is essential in the diagnostic work-up of myocardial infarction with non-obstructive coronary arteries (MINOCA) and also serves as an effective gatekeeper in suspected non-ST elevation myocardial infarction (NSTEMI) through the exclusion of mimickers such as myocarditis, thereby reducing the number of useless ICA. Moreover, CMR is supported by substantial evidence regarding its prognostic value in ACS patients. When available, myocardial perfusion imaging, using single photon emission tomography or positron emission tomography, has a valuable role in patients with suspected ACS and non-diagnostic ECG and biomarkers; in fact, it can detect inducible ischemia and prior infarction with a high NPV supporting safe discharge and reducing unnecessary admissions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>We aim to point out the role of non-invasive multimodal imaging in patients with confirmed or suspected ACS. By analyzing the available evidence and current guidelines, it\u2019s clear that these imaging techniques are especially useful in cases of low pre-test ACS probability, low-risk NSTEMI, in ruling out alternative diagnoses, and in specific diagnostic work-up such as MINOCA. In clinical practice, our goal is to provide practical recommendations for the clinicians on when and how to apply non-invasive imaging to reduce the number of ICA in order to minimize redundant, costly, and invasive diagnostic procedures that carry an inherent risk of complications.\u00a0<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p>Non-invasive imaging in the diagnostic pathway of suspected NSTE-ACS.\u00a0* This refers to patients with acute myocardial injury but low levels of cTn, low pre-test probability of CAD (no history of previous MI, known CAD or revascularizations) or with possible alternative causes of myocardial injury.\u2020 Depending on center expertise and availability, either stress echocardiography, rest\/stress SPECT\/PET, stress CT perfusion and stress CMR can also be used.<\/jats:p>\n                  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