The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low frequency (80-300 MHz) southern sky. Since beginning operations in mid 2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together 60+ programs recorded 20,000 hours producing 146 papers to date. In 2016 the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper we review the major results from the prior operation of the MWA, and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes, but also include ideas for directions outside these categories.