The advent of mobile devices, wearables and digital healthcare has unleashed a demand for accurate, reliable, and non-interventional ways to measure continuous blood pressure (BP). Many consumer products claim to measure BP with a cuffless device, but their lack of accuracy and reliability limit clinical adoption. Here, we demonstrate how multimodal feature datasets, comprising: (i) pulse arrival time (PAT); (ii) pulse wave morphology (PWM), and (iii) demographic data, can be combined with optimized Machine Learning (ML) algorithms to estimate Systolic BP (SBP), Diastolic BP (DBP) and Mean Arterial Pressure (MAP) within a 5 mmHg bias of the gold standard Intra-Arterial BP, well within the acceptable limits of the IEC/ANSI 80601-2-30 (2018) standard. Furthermore, DBP’s calculated using 126 datasets collected from 31 hemodynamically compromised patients had a standard deviation within 8 mmHg, while SBP’s and MAP’s exceeded these limits. Using ANOVA and Levene’s test for error means and standard deviations, we found significant differences in the various ML algorithms but found no significant differences amongst the multimodal feature datasets. Optimized ML algorithms and key multimodal features obtained from larger real-world data (RWD) sets could enable more reliable and accurate estimation of continuous BP in cuffless devices, accelerating wider clinical adoption.