Research on heatwaves has gained significant impetus over the past decade due to a warming planet and rapid 21st century urbanization. This study examines driving factors influencing heatwave trends and interannual variability across Southern California (SoCal) from 1950–2020. Inland urban areas of Los Angeles county are the most susceptible to heatwaves with strong increasing trends in frequency, duration, and intensity that are closely tied to nighttime warming. Coastal and rural areas are less impacted but show a significant increase in heatwave frequency over the past two decades. Heatwave nighttime temperatures combined with high humidity have been increasing at a rapid rate of ~1°C/decade since the 1980s—elevating heat stress and mortality risk to vulnerable urban communities. The increased nighttime humidity is associated with an anomalous moisture source off the coast of Baja California that has intensified over the past decade and is linked to ocean warming trends and changes in the California current system. Heatwaves are starting earlier and ending later in the year for urban regions. This augments public health risks and sets the stage for more intense fall wildfires by enhancing the drying of fuels. Droughts and heatwaves are strongly linked, particularly in inland urban and rural areas that have a high statistical probability of heatwaves increasing in frequency (42%), duration (26%), and daily mean temperature (2.2%) during severe drought conditions. Better understanding of heatwave climate drivers and underlying physical processes could help with prediction skill, in addition to providing effective data‐driven recommendations for mitigation efforts in SoCal's vulnerable urban regions. Plain Language Summary Heatwaves can have a devastating effect on society, infrastructure, and the environment. This study investigates driving factors associated with urbanization, nighttime warming and humidity, ocean dynamics, and droughts that influence heatwaves in Southern California. We show that inland urban heatwaves are rapidly increasing in frequency, duration, and intensity with a greater tendency toward more humid nighttime events—a trend likely to accelerate through the 21st century and linked to human‐induced climate change. Coastal and rural areas are less impacted but show a threefold increase in heatwave frequency over the past two decades. Heatwaves have a high probability of increasing by 42% in frequency and by 26% in duration during severe drought conditions. Heatwaves have significantly intensified over the past two decades. They occur later in the year during peak fire season, exposing densely populated regions to the risks of extreme heat, wildfire, and pollution. A better understanding of heatwave dynamics can improve heatwave predictions and help to develop local adaptation and mitigation strategies in vulnerable communities.