Authorities said flooding and rain-triggered landslides forced the Vietnam Railways Corporation to halt 25 passenger trains.
The company cancelled several North-South services and offered refunds or itinerary changes to affected travelers, according to state media.
Freight movements on the same corridor were also hit, with six cargo trains cancelled and 27 stranded along the route.
The operator estimated total economic losses at nearly 10 billion Vietnamese dong (about 398,000 US dollars).
Rescuers pulled stranded residents from rooftops of submerged homes as floodwaters swamped large parts of the region.
Heavy rain has pounded south-central provinces since late October, inundating popular tourist destinations through several rounds of flooding.
Parts of Nha Trang were under deep water, with AFP images showing whole blocks submerged and hundreds of cars flooded.
Business owner Bui Quoc Vinh, 45, said he remained safe in his 24th-floor Nha Trang apartment, while his ground-floor restaurants and shops were submerged by about a meter of water.
"I am worried about our furniture in my restaurants and shops, but of course I cannot do anything now," he told AFP.
"My staff have to take care of their flooded homes," he said, adding those homes were under two meters of water.
"I don't think the water is going to recede soon as the rain has not stopped."
State media reported that rescuers in Gia Lai and Dak Lak provinces used boats to pry open windows and break through roofs to reach stranded residents.
The environment ministry said 43 people had died across six provinces since Sunday, and rescue teams were still looking for nine missing.
More than 52,000 homes were flooded, nearly 62,000 people were evacuated, and major roads remained cut off by landslides.
About one million customers lost electricity, the ministry said.
Highland areas near Da Lat recorded up to 600 millimeters of rain since the weekend, triggering deadly landslides along mountain passes.
Hotel owner Vu Huu Son, 56, said landslides had blocked all but one road into the city.
"I don't think we have tourists now as they all left at the weekend before the rain and also cancelled their tours here," he told AFP.
A 100-metre section of the Mimosa Pass was blocked by a landslide late Wednesday, and two other routes were closed due to further risks, according to Tuoi Tre News.
State media reported that several train lines linking northern and southern Vietnam were suspended due to flooding.
Deputy Prime Minister Ho Quoc Dung ordered provincial leaders in Khanh Hoa, Dak Lak and Gia Lai to mobilise the army, police and other forces to "promptly relocate and evacuate people" to safe zones, a government statement said.
Rescuers delivered food and water to flooded hospitals in Quy Nhon in Binh Dinh province, state-run Thanh Nien reported, after patients and doctors survived on instant noodles and water for three days.
The weather bureau said the Ba River in Dak Lak surpassed a 1993 record at two locations early Thursday, while the Cai River in Khanh Hoa also hit a new high.
Hoang Phuc Lam, deputy head of the National Center for Hydrometeorological Forecasting, told state television the flooding worsened as persistent heavy rain added to already elevated water levels.
In Dak Lak, floodwaters swept away 100 barrels of sulfuric acid from a sugar factory, prompting the public security ministry to warn residents to avoid the hazardous liquid.
Vietnam’s statistics office said natural disasters left 279 people dead or missing and caused more than 2 billion US dollars in damage between January and October.
The country experiences intense rainfall from June to September, and scientists have linked increasingly severe weather events to human-driven climate change.
Rescue teams continued efforts on Thursday to reach people stranded in homes or on rooftops across central and southern provinces.
Coastal areas from Hoi An to Nha Trang were among the worst affected by the latest round of flooding and landslides.