Roukes’ thesis research at Cornell elucidated the electron–phonon bottleneck at ultra low temperatures;[1] the hot electron effect that is now recapitulated in texts on solid state transport physics.

[5] Roukes' other research efforts at Caltech have focused on thermal properties of nanostructures, semiconductor spintronics, and, more recently, nanobiotechnology.

[12] Among his groups' principal achievements at Caltech are development of the first nanoelectromechanical systems,[13] measurement of the quantum of thermal conductance,[14] first attainment of attogram mass resolution with a NEMS resonator,[15] first measurement of nanodevice motion at microwave frequencies,[16] discovery of the giant planar Hall effect in semiconducting ferromagnets,[17] observation and control of a single domain wall in a ferromagnetic semiconducting wire,[18] first demonstration of zeptogram-scale mass sensing,[19] first coupling of a qubit to a NEMS resonator,[20] and first demonstration of nanomechanical mass spectrometry of single protein molecules.

[21] Roukes has authored or co-authored highly cited general interest articles on nanophysics,[22] nanoelectromechanical systems,[23][24] spintronics,[25] and quantum electromechanics.

An electron micrograph of the quantum of thermal conductance device, taken by postdoc Keith Schwab and colorized by Roukes, was acquired for the permanent collection of the Museum of Modern Art in 2008.

[32] In 2016, Roukes founded the multi-institution Neurotech Alliance to disseminate state-of-the-art neurotechnology to the neuroscience research community.