Background: Isometric resistance training (IRT) has emerged as a promising non-pharmacological intervention for blood pressure (BP) management. Although current hypertension guidelines primarily recommend aerobic and dynamic resistance exercise, growing evidence indicates that IRT is an effective, feasible, and time-efficient alternative. This narrative review summarizes the current evidence on the efficacy, physiological mechanisms, and clinical applications of IRT. We reviewed randomized controlled trials, systematic reviews, and meta-analyses evaluating the effects of different IRT modalities, including isometric handgrip (IHG), isometric wall squat (IWS), and isometric leg exercise (ILE), on BP in normotensive individuals, patients with hypertension, and those with cardiovascular disease. Results: IRT consistently reduces resting systolic BP by approximately 5–8 mmHg and diastolic BP by 3–4 mmHg, effects comparable to those achieved with first-line antihypertensive therapy and at least equivalent to those of other exercise modalities. These benefits have been demonstrated across normotensive and hypertensive populations and appear largely independent of age, sex, medication use, and the muscle groups involved. Preliminary evidence also supports the feasibility and safety of appropriately prescribed IRT in selected patients with ischemic heart disease and heart failure with preserved ejection fraction. Proposed mechanisms include improvements in endothelial function, nitric oxide bioavailability, autonomic regulation, oxidative stress, arterial baroreflex sensitivity, and myocardial efficiency. In conclusion: IRT is an effective, safe, and practical adjunct to lifestyle modification for BP control, particularly in older adults and individuals with limited ability to perform conventional exercise. However, further large-scale randomized trials are needed to define the optimal exercise prescription, clarify the underlying mechanisms, and establish the role of IRT in patients with cardiovascular disease.